CN110049995A - 哺乳动物表达的新型人类免疫缺陷病毒包膜蛋白抗原 - Google Patents

哺乳动物表达的新型人类免疫缺陷病毒包膜蛋白抗原 Download PDF

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CN110049995A
CN110049995A CN201880003141.5A CN201880003141A CN110049995A CN 110049995 A CN110049995 A CN 110049995A CN 201880003141 A CN201880003141 A CN 201880003141A CN 110049995 A CN110049995 A CN 110049995A
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乔迪·梅尔顿威特
索丹尼·申
马克·鲍迈斯特
乔迪·贝里
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Krairuek Complex Diagnostic Solutions Co
Grifols Diagnostic Solutions Inc
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Abstract

本发明的多种实施方案涉及包含HIV包膜蛋白的1个‑10个或更多个表位和融合蛋白的多肽,其中该多肽缺少HIV gp41蛋白的跨膜结构域。这样的多肽可以在哺乳动物细胞例如人类细胞中表达,以产生例如可用于开发新型抗HIV抗体的多肽。本文描述的多肽和由此开发的新型抗体通常可用于医学诊断,并且它们还可以用于HIV的预防性和治疗性治疗。

Description

哺乳动物表达的新型人类免疫缺陷病毒包膜蛋白抗原
描述
本申请与经由EFS-Web作为ASCII文本文件的电子序列表一起提交。电子序列表以标题为SEQLIST1800393.txt的文件提供,所述文件被创建并最后保存于2018年11月15日,大小为501,813个字节。电子序列表的信息通过引用以其整体被并入本文。
领域
本公开内容涉及重组蛋白的领域。本公开内容的一些实施方案涉及包含HIVgp120或gp41蛋白的至少一个表位和融合蛋白的HIV包膜重组多肽。本公开内容还涉及用于测定包含HIV抗体的样品的方法和装置。
背景
HIV引起了全球性流行病,导致估计3500万人由于AIDS相关疾病而死亡。在2016年出现了估计180万新的HIV病例,并且全世界约3670万人受到感染。HIV是慢病毒属(lentivirus)亚组中逆转录病毒家族的成员,并且具有两种描述的类型:HIV-1和HIV-2。HIV-1比HIV-2更具传染性和毒性,并且HIV-1在全世界引起大多数HIV感染。
每个HIV病毒体包含编码9种基因和19种蛋白质的两个RNA拷贝。完整病毒体表面上仅有的蛋白质是由env基因编码的包膜糖蛋白。env基因的产物是约850个氨基酸的前体蛋白,被称为gp160。该蛋白质在内质网中被细胞蛋白酶弗林蛋白酶裂解成两种裂解产物gp120和gp41。gp120和gp41都以三聚体存在于细胞表面,以形成异二聚体“尖峰”。gp41是一种跨膜糖蛋白,其充当细胞外gp120的锚,它与细胞外gp120非共价结合。gp120含有用于淋巴细胞上细胞受体的结合位点,并且对于病毒进入细胞至关重要。
作为病毒体表面上仅有的蛋白质,gp120和gp41暴露被宿主免疫系统靶向的许多免疫显性表位。历史上这些蛋白质的形式已经被用于免疫测定,以捕获和检测针对它们发动的抗体,作为HIV感染的确认。
gp120和gp41可用于疫苗接种、诊断测定并可用于诊断测定的开发。重组gp120和gp41通常在酵母中产生,但是在酵母中gp120和gp41的产生是具有挑战性的,因为蛋白质可能错误折叠、聚集和/或累积异常翻译后修饰。此外,从酵母中纯化gp120和gp41呈现了一个艰难的多步骤过程。因此,用于产生gp120和gp41抗原的改进的组合物和方法是期望的。
概述
本发明的多种实施方案涉及重组多肽,所述重组多肽包含HIV包膜蛋白的至少一个表位和融合蛋白,其中重组多肽缺少跨膜结构域,并且融合蛋白包含不由HIV编码的氨基酸序列。
本发明的多种实施方案涉及重组多肽,所述重组多肽包含前导肽、融合蛋白、HIVgp120蛋白的至少一个表位和/或HIV gp41蛋白的至少一个表位;其中融合蛋白包含不由HIV编码的区域,所述区域选自由抗体的Fc结构域、p53结构域、GCN4结构域或网格蛋白结构域组成的组,并且其中重组多肽缺少跨膜结构域。
根据本发明的重组多肽缺少跨膜结构域,所述跨膜结构域具有选自由以下组成的组的氨基酸序列:SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:70、SEQ ID NO:71或SEQ ID NO:72。
根据本发明的重组多肽可以包含HIV包膜蛋白的多于一个表位。在一些实施方案中,重组多肽包含至少4个、5个、6个、7个、8个、9个或10个表位。在一些实施方案中,每个表位通过接头被连接至另一个表位,所述接头的氨基酸序列不由HIV编码。在一些实施方案中,将每个表位连接至另一个表位的接头包含以下中列出的氨基酸序列:SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:109、SEQ ID NO:110或SEQ IDNO:111。
多肽可以包含HIV包膜蛋白的多于一个表位,其中该多于一个表位中的每个表位通过不由HIV编码的氨基酸序列被连接至该多于一个表位中的另一个表位。例如,该多于一个表位中的每个表位可以通过接头被连接至该多于一个表位中的另一个表位。在一些实施方案中,该多于一个表位中的每个表位可以通过接头被连接至该多于一个表位中的另一个表位,例如,其中每个接头包括α螺旋或β链。该多于一个表位可以包括至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位。包含该多于一个表位的多肽可以包含以下中列出的氨基酸序列:SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:20、SEQ ID NO:21或SEQ ID NO:22,或可以包含与以下中列出的氨基酸序列具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列:SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ IDNO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:20、SEQ ID NO:21或SEQ IDNO:22。
多肽可以包含HIV gp120蛋白的一个或更多个表位、HIV gp41蛋白的一个或更多个表位、或HIV gp120蛋白和HIV gp41蛋白两者的一个或更多个表位。
在一些实施方案中,重组多肽包含以下中列出的氨基酸序列:SEQ ID NO:1、SEQID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ IDNO:8、SEQ ID NO:9、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ IDNO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ IDNO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ IDNO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:91、SEQ ID NO:92、SEQ IDNO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ ID NO:97、SEQ ID NO:98、SEQ IDNO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105或SEQ ID NO:106,或包含与以下中列出的氨基酸序列具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列:SEQ ID NO:1、SEQ IDNO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ IDNO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:91、SEQ ID NO:92、SEQ IDNO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ ID NO:97、SEQ ID NO:98、SEQ IDNO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105或SEQ ID NO:106。
在一些实施方案中,重组多肽的融合蛋白可以包含抗体Fc结构域。在一些实施方案中,融合蛋白包含抗体Fc结构域,抗体Fc结构域的氨基酸序列选自由以下组成的组:SEQID.NO:77、SEQ ID.NO:78、SEQ ID.NO:80或SEQ ID.NO:107。
在一些实施方案中,融合蛋白的抗体Fc结构域缺少寡聚化结构域,并且重组多肽是单体。这样的单体多肽可以包含以下中列出的氨基酸序列:SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ IDNO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:86、SEQ ID NO:88、SEQ ID NO:91、SEQ IDNO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ ID NO:97、SEQ IDNO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105或SEQ ID NO:106,或可以包含与以下中列出的氨基酸序列具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列:SEQID NO:1、SEQ ID NO:2、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ IDNO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ IDNO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ IDNO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:86、SEQ ID NO:88、SEQ IDNO:91、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ IDNO:97、SEQ ID NO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQID NO:103、SEQ ID NO:104、SEQ ID NO:105或SEQ ID NO:106。
在一些实施方案中,重组多肽的融合蛋白的抗体Fc结构域包括二聚化结构域。这样的重组多肽可以包含以下中列出的氨基酸序列:SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:87或SEQ ID NO:89,或可以包含与以下中列出的氨基酸序列具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列:SEQ ID NO:3、SEQ ID NO:4、SEQID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQID NO:87或SEQ ID NO:89。
在一些实施方案中,重组多肽的融合蛋白可以包含寡聚化结构域。在一些实施方案中,重组多肽的融合蛋白包含选自由p53结构域、GCN4结构域、网格蛋白结构域或抗体的Fc结构域(例如,包含抗体铰链区)组成的组的寡聚化结构域。这样的多肽可以包含以下中列出的氨基酸序列:SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:87或SEQ ID NO:89,或可以包含与以下中列出的氨基酸序列具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列:SEQ ID NO:3、SEQ IDNO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:87或SEQ ID NO:89。
多肽可以包含HIV gp120和/或HIV gp41的表位。多肽可以包含HIV gp120的1个、2个、3个、4个、5个、6个、7个、8个、9个或10个表位和/或HIV gp41的1个、2个、3个、4个、5个、6个、7个、8个、9个或10个表位。
多肽可以包含前导肽。在一些实施方案中,重组多肽的N-末端可以由前导肽组成,并且前导肽能够在重组多肽在哺乳动物细胞中翻译后将多肽移位到哺乳动物细胞(例如人类细胞)的细胞膜表面的外部。在一些实施方案中,前导肽包含SEQ ID NO:84中列出的氨基酸序列。
在一些实施方案中,重组多肽的融合蛋白是前导肽,但是融合蛋白通常不是前导肽。在其中融合蛋白是前导肽的实施方案中,重组多肽包含HIV gp120的表位和HIV gp41的表位,并且重组多肽缺少gp120/gp41裂解位点。这样的多肽可以包含以下中列出的氨基酸序列:SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:38,或可以包含与以下中列出的氨基酸序列具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列:SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:38。
在一些实施方案中,重组多肽还包含多组氨酸亲和标签。
本发明的一些实施方案涉及包含至少两种本文描述的多肽(例如本文描述的2种、3种或4种多肽)的寡聚多肽。寡聚多肽的每个多肽亚基可以具有相同的氨基酸序列,或者寡聚多肽可以包含具有不同氨基酸序列的多肽亚基。
本发明的一些实施方案涉及包含如本文描述的多肽或寡聚多肽的细胞,其中细胞是哺乳动物细胞,例如人类细胞。细胞可以是例如CHO、BHK、NS0、Sp2/0、COS、C127、HEK293、HT-1080、PER.C6、HeLa或Jurkat细胞。
本发明的一些实施方案涉及核酸,所述核酸包含编码任一个实施方案的多肽或寡聚多肽的核苷酸序列和可操作地连接至核苷酸序列的启动子。核苷酸序列可以被密码子优化以便在哺乳动物细胞(例如人类细胞)中表达。启动子可以能够驱动在哺乳动物细胞(例如人类细胞)中的表达。本发明的一些实施方案涉及包含核酸的细胞,所述核酸包含编码本文描述的多肽或寡聚多肽的核苷酸序列。细胞可以是克隆性细胞(例如大肠杆菌(E.coli))或表达性细胞(例如CHO、BHK、NS0、Sp2/0、COS、C127、HEK293、HT-1080、PER.C6、HeLa或Jurkat细胞)。
本发明的一些实施方案涉及用于测定包含抗HIV抗体的组合物的装置,所述装置包括固体支持物和如本文描述的多肽或寡聚多肽,其中多肽或寡聚多肽共价地或非共价地结合至固体支持物。组合物可以包含例如从人类患者获得的体液,诸如血液、血浆、血清或唾液。固体支持物可以是珠、膜、微量滴定板、多肽芯片或色谱柱的固相。
本发明的一些实施方案涉及免疫测定试剂,所述免疫测定试剂包含如本文描述的多肽或寡聚多肽,其中免疫测定试剂结合至固体支持物。在一些实施方案中,固体支持物是珠、膜、微量滴定板、多肽芯片或色谱柱的固相。
本发明的一些实施方案涉及产生抗体的方法,所述方法包括向动物施用如本文描述的多肽或寡聚多肽。方法还可以包括分离动物的产生抗体的细胞。方法还可以包括分离动物的核酸,其中该核酸编码抗体。
本发明的一些实施方案涉及测定包含抗体的样品的方法,所述方法包括使样品与如本文描述的多肽或寡聚多肽接触,以及确定抗体和多肽或寡聚多肽之间的结合亲和力。在一些实施方案中,结合亲和力可以是相对结合亲和力,其中结合亲和力是相对结合亲和力是因为它是相对于一种或更多种不同抗体的结合亲和力。
本发明的一些实施方案涉及从多于一种抗体中选择抗HIV抗体的方法,所述方法包括使如本文描述的多肽或寡聚多肽与包含多于一种抗体的组合物接触,以及鉴定相对于组合物中的其他抗体对多肽或寡聚多肽具有高结合亲和力的抗体,从而选择抗HIV抗体。
本发明的一些实施方案涉及预防或治疗人类患者中的HIV感染的方法,所述方法包括向患者施用如本文描述的重组多肽或寡聚多肽。
本发明的一些实施方案涉及从人类生物样品的供应物中选择生物样品的方法,所述方法包括从所述供应物中选择不包含与如在此描述的重组多肽或寡聚多肽形成抗原-抗体复合物的抗体的那些样品。
附图简述
图1包括多肽env_1至env_38、env_39至env_42和env_43至env_54的示意图,所述多肽在示例部分中被描述并且分别具有SEQ ID NO:1-38、SEQ ID NO:92至94和SEQ ID NO:95至106中列出的氨基酸序列。
图2是具有SEQ ID NO:1中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp120的多于一个表位。
图3是具有SEQ ID NO:2中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp120的多于一个表位。
图4是具有SEQ ID NO:5中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为p53四聚化结构域的融合蛋白,并且明亮部分包含HIV gp120的多于一个表位。
图5是具有SEQ ID NO:6中列出的氨基酸序列的重组多肽的预测结构的图像,所述重组多肽包括GCN4三聚化结构域和HIV gp120的多于一个表位。
图6是具有SEQ ID NO:7中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为网格蛋白三聚化结构域的融合蛋白,并且明亮部分包含HIVgp120的多于一个表位。
图7是具有SEQ ID NO:8中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp41的多于一个表位。
图8是具有SEQ ID NO:9中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp41的多于一个表位。
图9是具有SEQ ID NO:10中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp120表位。
图10是具有SEQ ID NO:13中列出的氨基酸序列的重组多肽二聚体的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIVgp120表位。
图11是具有SEQ ID NO:14中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp120表位(左)和HIV gp41表位(右)。
图12是具有SEQ ID NO:15中列出的氨基酸序列的重组多肽二聚体的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIVgp120表位(左)和HIV gp41表位(右)。
图13是具有SEQ ID NO:18中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且亮部分包含HIV gp41表位。
图14是具有SEQ ID NO:19中列出的氨基酸序列的重组多肽二聚体的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIVgp41表位。
图15是具有SEQ ID NO:21中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp41的多于一个表位和HIV gp120的多于一个表位。
图16是具有SEQ ID NO:22中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp120表位和HIV gp41的多于一个表位。
图17是具有SEQ ID NO:23中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV包膜蛋白表位。
图18是具有SEQ ID NO:24中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV包膜蛋白表位。
图19是具有SEQ ID NO:28中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV包膜蛋白表位。
图20是具有SEQ ID NO:29中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV包膜蛋白表位。
图21是具有SEQ ID NO:30中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV包膜蛋白表位。
图22是具有SEQ ID NO:31中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV包膜蛋白表位。
图23是具有SEQ ID NO:32中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含gp41表位。
图24是具有SEQ ID NO:33中列出的氨基酸序列的重组多肽的预测结构的图像,其中结构的黑暗部分包含作为抗体Fc结构域的融合蛋白,并且明亮部分包含HIV gp41表位。
图25是具有SEQ ID NO:34中列出的氨基酸序列的重组多肽的预测结构的图像,所述重组多肽包括HIV gp41表位和HIV gp120表位。
图26是具有SEQ ID NO:92中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp41表位,并且黑色包含接头。
图27是具有SEQ ID NO:93中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp41表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp120表位,并且黑色包含接头。
图28是具有SEQ ID NO:94中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp41表位,并且黑色包含接头。
图29是具有SEQ ID NO:95中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp41表位,并且黑色包含接头。
图30是具有SEQ ID NO:96中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp41表位,并且黑色包含接头。
图31是具有SEQ ID NO:97中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp41表位,并且黑色包含接头。
图32是具有SEQ ID NO:98中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV p24表位,并且黑色包含接头。
图33是具有SEQ ID NO:99中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV p24表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp120表位,并且黑色包含接头。
图34是具有SEQ ID NO:100中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV p24表位,并且黑色包含接头。
图35是具有SEQ ID NO:101中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV p24表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp120表位,并且黑色包含接头。
图36是具有SEQ ID NO:102中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV p24表位,并且黑色包含接头。
图37是具有SEQ ID NO:103中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV p24表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp120表位,并且黑色包含接头。
图38是具有SEQ ID NO:104中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV p24表位,并且黑色包含接头。
图39是具有SEQ ID NO:105中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV p24表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp120表位,并且黑色包含接头。
图40是具有SEQ ID NO:106中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp41表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp120表位,并且黑色包含接头。
图41是在还原(上图)和非还原(下图)条件下运行的4%-20%tris-甘氨酸TGXTM十二烷基硫酸钠聚丙烯酰胺(SDS-PAGE)凝胶的图像。凝胶用InstantBlueTM蛋白染色剂染色。每种凝胶的泳道从左至右被编号为1至9。第一个泳道包含分子量标志物,并且泳道2-9包含多肽env_1、env_2、env_3、env_4、env_5、env_8、env_9和env_10,它们被克隆并且然后在真核细胞中表达。多肽env_1、env_2、env_3、env_5、env_8、env_9和env_10以可检测的水平表达。
图42是在还原(上图)和非还原(下图)条件下运行的4%-20%tris-甘氨酸TGXTMSDS-PAGE凝胶的图像。凝胶用InstantBlueTM蛋白染色剂染色。每种凝胶的泳道从左至右被编号为1至9。第一个泳道包含分子量标志物,并且泳道2-9包含多肽env_11、env_12、env_13、env_14、env_15、env_16、env_17和env_18,它们被克隆并且然后在真核细胞中表达。每种多肽能够以可检测的水平表达。
图43是在https://www.hiv.lanl.gov/content/immunology/maps/ab/gp160.html可得的LANL gp160AB表位图的2017年10月19日版本的一部分图像。
图44是具有SEQ ID NO:91中列出的氨基酸序列的重组多肽的预测结构的图像,其中浅灰色部分包含HIV gp120表位,中灰色包含抗体Fc结构域,深灰色包含HIV gp41表位,并且黑色包含接头。
详细说明
HIV-1将包膜蛋白(gp120和gp41)表达为三聚体结构,其中gp41嵌入膜中并且gp120处于各个gp41蛋白的顶部。相比于现有技术蛋白,本发明的多种实施方案包括用于诊断用途的若干明显优势。实施方案的一些方面涉及寡聚化结构域,其再创建不能使用单体蛋白产生的表位的实际的二级、三级和四级构象。实施方案的其他方面涉及通过使用哺乳动物细胞产生的改进,哺乳动物细胞允许正确的翻译后修饰,这对于表位特别是对于gp120表位至关重要,但这在酵母(例如,酵母属(Saccharomyces)或毕赤酵母属(Pichia))或大肠杆菌中不可再现。所描述的实施方案的多个方面涉及这一发现,即在哺乳动物细胞中产生的并且缺少跨膜结构域的重组HIV包膜多肽相对于全长重组HIV包膜蛋白显示出改进的特性。
基于迄今为止由许多诊断公司制备和使用的酵母形式需要苛刻的去垢剂(例如十二烷基硫酸钠)来溶解多肽,并且包括大的、不相关的融合蛋白(例如超氧化物歧化酶)以帮助表达的事实,这些多肽被设计以更好地模拟天然HIV包膜结构并且改进重组HIV包膜多肽的溶解性和收率。在哺乳动物细胞中产生的HIV多肽采用天然构象。如本文描述的多种融合结构域的使用也改进了HIV包膜溶解性和稳定性,并且有助于纯化。
天然HIV gp120/gp41蛋白的结构部分地依赖于三个gp41亚基的三个跨膜结构域嵌入脂质双层中,并且缺少跨膜结构域的重组HIV gp120或gp41多肽是否可以折叠成天然样的状态是未知的和不可预测的。本文描述的大多数多肽在无去垢剂的存在下是可溶的,并且因此能够折叠成天然样的三维构象。
天然HIV gp120/gp41蛋白形成异寡聚体四级结构。多种实施方案包括寡聚多肽,所述寡聚多肽包括复制天然HIV gp120/gp41的寡聚体四级结构的亚基。天然HIV gp120/gp41蛋白的四级结构部分地由其在膜中的定向来界定,所述定向由gp41亚基的跨膜螺旋来固定。缺少跨膜螺旋的重组HIV gp120/gp41多肽缺少使单体定向的组分。一些公开的多肽包含不存在跨膜结构域的寡聚化结构域,该寡聚化结构域将多肽亚基定向为促进天然样的四级结构。
I.多肽
本发明的多种实施方案包括多肽,所述多肽包含HIV包膜蛋白的至少一个结构域。如本文公开的多肽可以包含HIV包膜蛋白的至少两个结构域。HIV包膜蛋白优选地是HIV-1包膜蛋白,其比HIV-2更具传染性和毒性,并且它引起全世界大多数HIV感染。在一些实施方案中,HIV包膜蛋白是HIV-2包膜蛋白。
在本文描述的实施方案中特征化的多肽均是重组多肽,即它们包含不共存于天然存在的多肽中的两种或更多种氨基酸序列。因此,术语“多肽”和“重组多肽”在本文中可互换地使用。
完整HIV病毒体表面上的仅有蛋白质是由env基因编码的包膜糖蛋白。env基因产物是一种约850个氨基酸的前体蛋白,被称为gp160,其在本文中也被称为HIV包膜蛋白。HIV包膜蛋白的示例性氨基酸序列在SEQ ID NO:39-62中列出,并且其他可以在例如https://www.hiv.lanl.gov/components/sequence/HIV/search/search.html或在https://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.html找到(例如,通过选择“比对类型”为“Web(所有完整序列)”和“年份”为“2016”)。
HIV包膜蛋白的氨基酸序列还可以例如通过搜索NCBI的蛋白质数据库的“gp160”或“HIV包膜蛋白”(例如,在https://www.ncbi.nlm.nih.gov/protein)来确立。
术语“多肽”指的是具有任何长度的氨基酸序列的分子,但是如在本文描述的权利要求书和实施方案中使用的术语“多肽”需要足够长的氨基酸序列以包含HIV包膜蛋白表位(即至少8个氨基酸)和融合蛋白。如本文使用的术语“结构域”类似地指的是足够长以独立地折叠的氨基酸序列。结构域可以包括表位(即至少8个氨基酸),但是结构域不需要包含表位。跨膜结构域可以包括8个或更多个氨基酸,并且例如,如果结构域不是抗原性的,则跨膜结构域还可以不包括表位。
根据本文的实施方案的多肽通常包含200个至1000个氨基酸,例如约200个至约400个、约300个至约500个、约400个至约600个、约500个至约700个、约600个至约800个、约700个至约900个或约800个至约1000个氨基酸。多肽的氨基酸通常通过肽键连接,例如,因为这些多肽通常通过核糖体上RNA的翻译来产生。
实施方案的多肽通常具有约20,000道尔顿至约100,000道尔顿,例如约20,000道尔顿至约40,000道尔顿、约30,000道尔顿至约50,000道尔顿、约40,000道尔顿至约60,000道尔顿、约50,000道尔顿至约70,000道尔顿、约60,000道尔顿至约80,000道尔顿、约70,000道尔顿至约90,000道尔顿或约80,000道尔顿至约100,000道尔顿的分子量。
实施方案的多肽通常具有约5至约10,例如约5.5至约8.5、约5.0至约7.0、约6.0至约8.0、约7.0至约9.0、约5.0至约6.0、约5.5至约6.5、约6.0至约7.0、约6.5至约7.5、约7.0至约8.0、约7.5至约8.5、约8.0至约9.0、约8.5至约9.5或约9.0至约10.0的等电点(pI)。
实施方案的多肽缺少gp41跨膜结构域,即,每个多肽缺少由SEQ ID NO:63-72中的任一个编码的氨基酸序列。实施方案的多肽可以缺少与由SEQ ID NO:63-72编码的氨基酸序列具有至少60%、67%、75%、80%、85%、90%或95%序列同一性的氨基酸序列。实施方案的多肽可以缺少嵌入生物膜(即脂质双层)的氨基酸序列。氨基酸序列可能嵌入生物膜的概率可以使用本领域已知的许多不同方法的任一种来确定,所述方法包括例如基于Ez深度依赖性潜力(Ez Depth-dependent Potential)的计算(Senes等人,J.Molecular Biology366(2):436(2007))。
本发明的多肽可以缺少全长HIV包膜蛋白的gp120/gp41裂解位点。
A.HIV包膜蛋白的表位
实施方案包括包含HIV包膜蛋白的至少一个表位的多肽。如本文公开的多肽可以包含HIV包膜蛋白的至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位。多肽可以包含HIV包膜蛋白的多于一个表位。多肽可以包含HIV包膜蛋白的多于一个表位,其中该多于一个表位包括至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位。
如在说明书和权利要求书中使用的术语“表位”指的是可以特异性结合抗体的抗原结合位点的至少8个连续氨基酸的序列。表位可以包括例如至少9个、10个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个连续氨基酸。
表位可以由在SEQ ID NO:39-62中的任一个中发现的至少8个、9个、10个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个连续氨基酸的氨基酸序列组成,SEQ IDNO:39-62是HIV包膜蛋白的序列,只要该序列不包含被标识为SEQ ID NO:63-72的跨膜结构域的N-末端或C-末端。实施方案的多肽可以包含多于一个表位,其中该多于一个表位中的每个表位由在SEQ ID NO:39-62中的任一个中发现的至少8个、9个、10个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个连续氨基酸的氨基酸序列组成,只要该序列不包含被标识为SEQ ID NO:63-72的跨膜结构域的N-末端或C-末端。该多于一个表位中的每个表位可以具有不同的氨基酸序列,或者每个表位可以具有相同的氨基酸序列。实施方案的多肽可以包含HIV包膜蛋白的至少1个、2个、3个、4个、5个、6个、7个、8个、9个或10个表位,其中每个表位由在SEQ ID NO:39-62中的任一个中发现的至少8个、9个、10个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个连续氨基酸的氨基酸序列组成,只要该序列不包含被标识为SEQ ID NO:63-72的跨膜结构域的N-末端或C-末端。
HIV包膜蛋白的许多变体是已知的。因此,表位可以由与在SEQ ID NO:39-62(它们是HIV包膜蛋白的序列)中的任一个中发现的至少8个、9个、10个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个连续氨基酸具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列组成,只要该序列不包含被标识为SEQ ID NO:63-72跨膜结构域的N-末端或C-末端。实施方案的多肽可以包含多于一个表位,其中该多于一个表位中的每个表位由与在SEQ ID NO:39-62中的任一个中发现的至少8个、9个、10个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个连续氨基酸具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列组成,只要该序列不包含被标识为SEQ ID NO:63-72的跨膜结构域的N-末端或C-末端。多于一个表位中的每个表位可以具有不同的氨基酸序列,或者每个表位可以具有相同的氨基酸序列。实施方案的多肽可以包含HIV包膜蛋白的至少1个、2个、3个、4个、5个、6个、7个、8个、9个或10个表位,其中每个表位由与在SEQ ID NO:39-62中的任一个中发现的至少8个、9个、10个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个连续氨基酸具有至少约80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列组成,只要该序列不包含被标识为SEQ ID NO:63-72的跨膜结构域的N-末端或C-末端。
在其中多肽包含HIV包膜蛋白的多于一个表位的实施方案中,HIV包膜蛋白的表位可以是相同的表位或不同的表位。
多肽(或多于一个表位)可以包括存在于不同的HIV包膜蛋白(例如,选自SEQ IDNO:39-62的不同氨基酸序列)中的表位,或者多肽(或多于一个表位)可以包括每一个都存在于相同的HIV包膜蛋白中的表位。
HIV包膜蛋白的表位是熟知的。HIV包膜蛋白的表位可以例如从在https://www.hiv.lanl.gov/content/immunology/maps/ab/gp160.html可得的LANL gp160 AB表位图中选择。LANL gp160 AB表位图的2017年10月19日版本的一部分在图43中再现,并且本发明的多种实施方案以LANL gp160AB表位图中描述的表位为特征。
本发明的多个方面涉及包含HIV包膜蛋白的新型表位的多肽。在一些实施方案中,多肽包含HIV包膜蛋白的至少一个表位,其中至少一个表位包括在LANL gp160 AB表位图中未被鉴定的表位。多肽可以包含例如表位或多于一个表位,其中每个表位是在SEQ ID NO:39-62中的任一个中发现的至少8个连续氨基酸的随机选择的氨基酸序列。
表位可以是HIV gp120蛋白或HIV gp41蛋白的表位。多肽可以包含HIV gp120蛋白和/或HIV gp41蛋白的表位。多于一个表位可以包括HIV gp120蛋白和/或HIV gp41蛋白的表位。
多肽的表位侧翼可以为天然HIV包膜蛋白的氨基酸序列。例如,多肽可以包含HIV包膜蛋白的至少两个表位,其中至少两个表位中的两个表位通过HIV包膜蛋白的天然氨基酸序列连接。
多肽可以包含HIV包膜蛋白的至少两个表位,其中至少两个表位中的两个表位通过在不存在于天然存在的HIV包膜蛋白中的氨基酸序列连接。例如,多肽可以包含至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位,其中至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位中的2个、3个、4个、5个、6个、7个、8个、9个或10个表位通过不存在于天然存在的HIV包膜蛋白中的氨基酸序列连接。多肽可以包含至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位,其中至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位中的2个表位通过存在于天然存在的HIV包膜蛋白中的氨基酸序列连接。
在一些实施方案中,多肽包含HIV包膜蛋白的多于一个表位,其中该多于一个表位中的每个表位通过不由HIV编码的氨基酸序列被连接至该多于一个表位中的另一个表位。术语“接头”或“间隔物”可以在本文中使用以指连接本文描述的重组多肽的至少两个表位的所述氨基酸序列。
B.接头
多于一个表位中的每个表位可以通过接头或间隔物被连接至多于一个表位中的另一个表位。多于一个表位中的每个表位可以通过接头或间隔物被连接至多于一个表位中的一个或两个其他的表位。接头或间隔物指的是设计的氨基酸序列,其通常通过肽键连接并且具有确定的二级结构或是固有地无序的。术语“接头”和“间隔物”在本文中可互换地使用。接头可以包括形成α螺旋或β链的氨基酸序列(例如,其中β链与其他β链结合以形成β片层)。接头可以包含α螺旋或β片层。
接头可以由具有形成α螺旋的高倾向的连续氨基酸(例如丙氨酸)的序列组成,其可以任选地包括N-末端螺旋加帽基序(例如丝氨酸-脯氨酸-谷氨酸)和/或在i位和i+3/4位的电荷交替的氨基酸(例如,在i位的谷氨酸和在i+3位或i+4位的赖氨酸)。具有形成α螺旋的高倾向的示例性接头在SEQ ID NO:73(AEAAAKEAAAKA)中列出。
接头可以由具有形成β链的高倾向的连续氨基酸例如“β支链的”氨基酸(例如,缬氨酸、异亮氨酸、苏氨酸)的序列组成,但是具有形成β链的高倾向的连续氨基酸的其他序列是本领域已知的并且可以被选择以例如设计β片层。具有形成β链的高倾向的示例性接头在SEQ ID NO:74(TWIQNPGTKWYQNPGTKIYT)中列出。在一些实施方案中,多肽包含β片层,其中β片层的至少两条β链通过包含HIV包膜蛋白的表位的氨基酸序列连接。例如,多肽可以包含含有至少三条β链的β片层,其中第一条β链通过包含HIV包膜蛋白的第一表位的氨基酸序列被连接至第二条β链,并且第三条β链通过HIV包膜蛋白的第二表位被连接至第四条β链(即,其中第一条、第二条、第三条和第四条β链组成三条或四条β链(例如,第三条β链和第一条或第二条β链是相同的β链,或者第一条、第二条、第三条和第四条β链中的每一个是不同的β链),并且其中第一表位和第二表位可以任选地具有相同或不同的氨基酸序列)。
固有地无序的接头可以由具有高度结构无序的连续氨基酸的序列组成。固有地无序的接头通常包括至少一个甘氨酸和/或至少一个脯氨酸,所述甘氨酸缺少R基团并且因此具有比所有其他天然存在的氨基酸更易接近的构象,所述脯氨酸具有与其主链N形成环的R基团并且因此具有比所有其他天然存在的氨基酸更少的容易接近的构象。甘氨酸通过将熵(entropy)引入多肽的二级结构中来增加结构无序性,并且脯氨酸通过将熵引入多肽的二级结构中来增加结构无序性。固有地无序的接头还可以包括其他小氨基酸(例如丝氨酸、丙氨酸)和亲水性氨基酸。固有地无序的接头的氨基酸可以选自例如甘氨酸、脯氨酸、丙氨酸、丝氨酸、天冬酰胺、天冬氨酸、谷氨酰胺、谷氨酸、赖氨酸和精氨酸。示例性的固有地无序的接头包括在SEQ ID NO:75(SGSGASGS)、SEQ ID NO:76(PSGP)、SEQ ID NO:109(GGGGSGGGGSGGGGS)或SEQ ID NO:110(GGGGSGGGGSGGGGSGGGGSGGGGS)中列出的氨基酸序列,但是固有地无序的接头的精确的氨基酸序列没有特别限制。
柔性接头可以由通常包括至少一个甘氨酸、至少一个脯氨酸和至少一个丝氨酸的连续氨基酸的序列组成。示例性柔性接头包括在SEQ ID NO:111(GGGPS)中列出的氨基酸序列,尽管柔性接头的精确的氨基酸序列没有特别限制。
多于一个表位(或至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位)中的两个表位可以通过接头连接,其中接头包括α螺旋、β链、固有地无序的氨基酸序列或柔性氨基酸序列。多于一个表位(或至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位)中的每个表位可以通过接头被连接至多于一个表位(或至少2个、3个、4个、5个、6个、7个、8个、9个或10个表位)中的另一个表位,其中接头包括α螺旋、β链、固有地无序的氨基酸序列或柔性氨基酸序列。
尽管一些天然存在的氨基酸序列可以用作合适的接头或可以用于设计合适的接头,但接头通常不存在于在天然存在的HIV包膜蛋白,并且接头通常是自然界中不存在的。
接头可以包含约1个至30个氨基酸,例如约2个至25个、约3个至20个、约4个至16个、或约1个、2个、3个、4个、5个、6个、7个、8个、9个、10个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个氨基酸。
C.融合蛋白
实施方案的多肽通常包含融合蛋白,融合蛋白包含不存在于天然存在的HIV包膜蛋白中的氨基酸序列。融合蛋白可以包含不由HIV编码的区域,所述区域选自由以下组成的组:抗体的Fc结构域、p53结构域、GCN4结构域或网格蛋白结构域。融合蛋白优选地是至少20个氨基酸,例如至少30个、40个、50个、60个、70个、80个、90个、100个、110个、120个、130个、140个、150个、160个、170个、180个、190个或200个氨基酸或约20个至500个、约50个至约400个或约75个至约250个氨基酸的序列,但是融合蛋白的精确长度没有特别限制。
如本文中使用的术语“融合蛋白”并不指的是从多肽分离的独立的(discrete)蛋白。而是,术语“融合蛋白”指的是包含结构和/或功能特性的氨基酸序列,所述结构和/或功能特性通常可用于蛋白表达、纯化、寡聚化和/或稳定性。编码多肽的基因通常编码与多肽的其余部分符合读框(in-frame)的融合蛋白,而在融合蛋白和多肽的其他部分之间没有终止密码子;融合蛋白通常由mRNA被翻译为多肽的部分;并且融合蛋白通常通过一个或更多个天然肽键被连接至多肽的其他部分。
融合蛋白通常具有功能性质。例如,融合蛋白可以起将多肽与另一种多肽寡聚化的作用。在一些实施方案中,融合蛋白简单地增加多肽的稳定性,例如,多肽可以包含抗体Fc结构域,其可以增加多肽的稳定性。稳定性可以涉及多肽的降解、多肽的折叠和/或多肽的聚集,例如,融合蛋白可以增加多肽关于降解的半衰期、增加多肽(或寡聚多肽)的天然折叠的稳定性、和/或降低多肽形成聚集体的倾向。
融合蛋白通常具有确定的二级结构和确定的三级结构和/或四级结构。融合蛋白可以包括GCN4的一部分。融合蛋白可以包括例如,抗体Fc结构域的一部分,抗体Fc结构域的该部分具有确定的二级结构和三级结构,但缺少四级结构(例如,因为Fc结构域片段缺少铰链区和允许抗体形成二聚体或更高级寡聚体的其他元件)。融合蛋白可以包括例如,抗体Fc结构域的一部分,抗体Fc结构域的该部分具有确定的二级结构、三级结构和四级结构。
融合蛋白可以以单体存在,即,当折叠成其天然构象时,融合蛋白可以具有针对自身缔合的高解离常数。如例如在pH 7的磷酸盐缓冲盐水中确定的,高解离常数(KD)可以是例如>10mM、>1mM或>100μM,。
融合蛋白可以以寡聚体存在,例如,当折叠成其天然构象时,融合蛋白可以具有针对自身缔合的低解离常数。如例如在pH 7的磷酸盐缓冲盐水中确定的,低解离常数(KD)可以是例如<100μM、<10μM或<1μM,。因为融合蛋白例如诸如通过两个半胱氨酸之间的二硫键直接地、或诸如通过化学交联剂间接地被共价地连接至一种或更多种其他融合蛋白,所以融合蛋白可以以寡聚体存在。因为融合蛋白例如经由生物素-链霉亲和素相互作用被非共价地连接至一种或更多种其他融合蛋白,所以融合蛋白可以以寡聚体存在。
融合蛋白可以包含寡聚化结构域。寡聚多肽,例如二聚体多肽,对于开发针对天然gp120/gp41复合物的抗体可以是优异的,因为天然gp120/gp41以异二聚体的三聚体存在。寡聚化结构域还可用于定向多肽,从而复制天然样四级结构。
示例性寡聚化结构域包括抗体Fc结构域的氨基酸序列。抗体Fc结构域可以增加多肽在表达细胞中的表达和/或分泌。此外,由抗体Fc结构域形成的二聚体多肽通常增加多肽的体内半衰期。Fc结构域还可以定向寡聚多肽的亚基,从而在功能上补偿一个或更多个gp41跨膜螺旋的缺乏。铰链区的使用或省略可以分别形成二聚体或单体Fc融合物。
抗体Fc结构域的物种可以基于多肽或寡聚多肽的期望用途来选择。例如,抗体Fc结构域的物种可以被选择为使得特定试剂在测定中靶向或忽略抗体Fc结构域。例如,如果在测定中不使用抗小鼠第二抗体来检测其他小鼠抗体,则小鼠Fc结构域可以是有用的。类似地,小鼠Fc结构域可以用于检测具有抗小鼠“第二”抗体的多肽。对于体内使用,Fc结构域的物种可以被选择以匹配宿主,例如,降低宿主针对Fc结构域发动免疫应答的可能性。例如,小鼠Fc结构域可以用于在小鼠中产生小鼠抗HIV包膜蛋白抗体。Fc结构域的物种可以是人、小鼠、兔、大鼠、仓鼠、豚鼠、山羊、绵羊、马、鸡或前述物种的嵌合体,但是Fc结构域的物种没有特别限制。抗体Fc结构域的物种可以是小鼠IgG Fc结构域。示例性抗体Fc结构域是小鼠IgG1 Fc结构域或小鼠IgG2 Fc结构域。
示例性融合蛋白是小鼠IgG1 Fc结构域或小鼠IgG2 Fc结构域,其缺少铰链区并且因此不寡聚化。
单体小鼠IgG2 Fc结构域可以具有SEQ ID NO:77(APNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISKPKGSVRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNYKNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTPGK)中列出的氨基酸序列或可以具有与SEQ IDNO:77中列出的氨基酸序列具有至少约95%、96%、97%、98%或99%序列同一性的氨基酸序列。
另一种示例性融合蛋白是包含铰链区的小鼠IgG2Fc结构域,铰链区允许包含该融合蛋白的多肽二聚化。二聚体小鼠IgG2Fc结构域可以具有SEQ ID NO:78(PRGPTIKPCPPCKCPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDV SEDDPDVQISWFVNNVEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISKPKGSVRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNYKNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTPGK;其由N-末端铰链区PRGPTIKPCPPCKCP(SEQ ID NO:79)紧接着SEQ ID NO:77中列出的Fc结构域氨基酸序列组成)中列出的氨基酸序列或可以具有与SEQ ID NO:78中列出的氨基酸序列具有至少约95%、96%、97%、98%或99%序列同一性的氨基酸序列。
单体小鼠IgG1 Fc结构域可以具有SEQ ID NO:80(VPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPG)中列出的氨基酸序列或可以具有与SEQ ID NO:80中列出的氨基酸序列具有至少约95%、96%、97%、98%或99%序列同一性的氨基酸序列。
另一种示例性融合蛋白是包含铰链区的小鼠IgG1 Fc结构域,铰链区允许包含该融合蛋白的多肽二聚化。二聚体小鼠IgG1 Fc结构域可以具有SEQ ID NO:107(VPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPG;其由N-末端铰链区VPRDCGCKPCICT(SEQ ID NO:108)紧接着SEQ ID NO:80中列出的Fc结构域氨基酸序列组成)中列出的氨基酸序列或可以具有与SEQ ID NO:107中列出的氨基酸序列具有至少约95%、96%、97%、98%或99%序列同一性的氨基酸序列。
示例性融合蛋白可以包含Fc结构域,该Fc结构域缺少具有SEQ ID NO:77或SEQ IDNO:80中列出的氨基酸序列的寡聚化结构域,并且因此重组多肽是单体。示例性融合蛋白可以包含Fc结构域,该Fc结构域包括具有SEQ ID NO:78或SEQ ID NO:107中列出的氨基酸序列的二聚化结构域,并且因此重组多肽是二聚体。
由于纯化包含Fc结构域的多肽的方法是熟知的,因此Fc结构域也可以帮助多肽的纯化。
另一种示例性融合蛋白是p53四聚化结构域。p53四聚化结构域可以具有SEQ IDNO:81(KPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG)中列出的氨基酸序列或可以具有与SEQ ID NO:81中列出的氨基酸序列具有至少约95%、96%、97%、98%或99%序列同一性的氨基酸序列。
另一种示例性融合蛋白是GCN4三聚化结构域。GCN4三聚化结构域可以具有SEQ IDNO:82(GYIPEAPRDGQAYVRKDGEWVLLSTFL)中列出的氨基酸序列或可以具有与SEQ ID NO:82中列出的氨基酸序列具有至少约95%、96%、97%、98%或99%序列同一性的氨基酸序列。包含GCN4样序列的融合蛋白可以被设计成例如平行三聚体,其对应于天然gp120/gp41三聚体的拓扑学。可选择的GCN4样序列可以如本领域已知的来设计,以根据本领域已知的方法制备具有平行或反向平行结构的二聚的、三聚的和四聚的寡聚体(参见例如,Harbury,Zhang,Kim,和Alber,“A switch between two-,three-,and four-stranded coiledcoils in GCN4leucine zipper mutants”,Science(1993)262:1401)。除平行三聚体之外的寡聚体可以用于开发靶向新型HIV包膜蛋白抗原的抗体。
另一种示例性融合蛋白是网格蛋白三聚化结构域。网格蛋白三聚化结构域可以具有SEQ ID NO:83(GSHMWKQSVELAKKDSLYKDAMQYASESKDTELAEELLQWFLQEEKRECFGACLFTCYDLLRPDVVLELAWRHNIMDFAMPYFIQVMKEYLTKV)中列出的氨基酸序列或可以具有与SEQ ID NO:83中列出的氨基酸序列具有至少约95%、96%、97%、98%或99%序列同一性的氨基酸序列。
其他寡聚化结构域是本领域熟知的,并且寡聚化结构域的具体选择没有特别限制。例如,链霉亲和素可以是特别有用的寡聚化结构域,因为它形成四聚体并且还结合生物素,生物素可以帮助纯化并且还可以用于各种测定。
实施方案的融合蛋白不包括超氧化物歧化酶,超氧化物歧化酶通常用于制备重组HIV包膜蛋白,即,本发明的多肽缺少对应于超氧化物歧化酶的氨基酸序列。
D.前导肽序列
本文公开的多肽通常包含前导肽序列以有利于多肽跨越表达载体的细胞膜移位,所述表达载体例如哺乳动物细胞,尤其是人类细胞。然而,例如,如果前导肽序列通过酶裂解或化学裂解从多肽中裂解,则多肽可以缺少前导肽序列。合成所产生的多肽可以类似地缺少前导肽序列。
前导肽序列通常被包含在多肽的N-末端。前导肽序列优选地足以在真核细胞(例如哺乳动物细胞,诸如人类细胞)中翻译多肽后将多肽移位到真核细胞的细胞表面膜的外部,尽管多肽的其他序列基序也可以帮助移位。
示例性前导肽序列具有SEQ ID NO:84(MYRMQLLSCIALSLALVTNS)中列出的氨基酸序列,其是人类白细胞介素-2前导肽序列。该充分表征的序列能够将多肽移位到人类细胞和其他哺乳动物细胞两者之外。
在一些实施方案中,本文公开的多肽的前导肽是多肽的融合蛋白。在一些实施方案中,多肽包含HIV gp120的表位和HIV gp41的表位,并且多肽缺少gp120/gp41裂解位点。
前导肽序列通常不衍生自HIV包膜蛋白,但是在一些实施方案中,前导肽序列是HIV包膜蛋白的信号序列。
E.亲和标签
多肽可以任选地包括亲和标签。亲和标签可用于纯化,并且它们还可以用于利用多肽的测定中。示例性亲和标签包括多组氨酸、几丁质结合蛋白、麦芽糖结合蛋白、Strep-标签、谷胱甘肽-S-转移酶、FLAG-标签、V5-标签、Myc-标签、HA-标签、NE-标签、AviTag、钙调蛋白-标签、聚谷氨酸、S-标签、SBP-标签、Softag 1、Softag 3、TC标签、VSV-标签、Xpress标签、Isopeptag、SpyTag、SnoopTag、生物素羧基载体蛋白、绿色荧光蛋白-标签、HaloTag、Nus-标签和硫氧还蛋白-标签,但是亲和标签的选择没有特别限制。然而,例如,如果亲和标签在使用后被去除或如果使用不需要亲和标签的策略纯化多肽,则多肽可以缺少亲和标签。示例性亲和标签是多组氨酸,其通常包括包含六个连续组氨酸的氨基酸序列(SEQ IDNO:85)。另一种示例性亲和标签是包含4个和8个之间的连续组氨酸的多组氨酸。
F.示例性多肽序列
在本文描述的实施方案中被特征化的重组多肽可以包含前导肽、融合蛋白、HIVgp120蛋白的至少一个表位和/或HIV gp41蛋白的至少一个表位,其中重组多肽缺少跨膜结构域,并且其中融合蛋白包含不由HIV编码的区域。
本文公开的种类的多肽可以具有以下中列出的氨基酸序列:SEQ ID NO:1、SEQ IDNO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ IDNO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ IDNO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ IDNO:38、SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89、SEQ ID NO:91、SEQ IDNO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ ID NO:97、SEQ IDNO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105或SEQ ID NO:106。多肽可以具有与以下中列出的氨基酸序列具有至少约85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99.5%序列同一性的氨基酸序列:SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:86、SEQID NO:87、SEQ ID NO:88、SEQ ID NO:89、SEQ ID NO:91、SEQ ID NO:92、SEQ ID NO:93、SEQID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ ID NO:97、SEQ ID NO:98、SEQ ID NO:99、SEQID NO:100,SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105或SEQ ID NO:106,即,其中多肽的完整氨基酸序列不是天然存在的氨基酸序列。
II.被HIV-1和HIV-2感染的免疫生物学
取决于宿主的健康和遗传组成,被HIV感染导致免疫系统以多种方式之一响应。通常,在HIV经由感染CD4+T细胞进入宿主后,它开始复制并产生新的病毒颗粒,病毒颗粒从裂解的细胞释放到血流中。在该包膜病毒的表面上的是以稀疏散布的三聚体尖峰的“包膜相关蛋白”gp120和gp41。然而,处于gp41蛋白顶部的gp120蛋白倾向于从病毒(可能是毒株依赖性的)脱落,并且该脱落被本领域中一些人认为作为诱饵蛋白起作用。因此,gp41被暴露为用于宿主抗体应答的第一个初始表面靶。事实上,绝大多数HIV+患者对gp41部分发展强烈的抗体应答,并且这就是为什么许多诊断公司使用的在酵母中表达的以往的包膜蛋白(例如Env13、Env31和Env70)基本上由gp41序列组成,仅具有gp120的小片段。对于大多数感染HIV并且已经发动抗体应答的患者,该蛋白在约90%-98%的时间显示出抗体反应性。小百分比的非反应性患者对gp120和/或p24抗原显示出可测量的抗体应答。
在一些方面中,实施方案包括寡聚多肽,所述寡聚多肽包含与如本文描述的p24或p26(HIV-2)多肽(亚基)融合的相关gp120蛋白。在一些实施方案中,寡聚多肽是二聚体多肽,即包含两个亚基的寡聚多肽,其中每个亚基是本文描述的多肽。如在没有修饰词“寡聚”、“二聚”或其他明确提及多亚基形式的情况下使用的术语“多肽”指的是单体多肽,其可以存在或可以不存在于寡聚体例如二聚体、三聚体或四聚体中。这些蛋白可以用于血浆、血清或全血中抗体的前沿筛选(frontline screening),或用于诊断目的或用于证实性测定。
在一些方面中,实施方案包括多肽,所述多肽包含100%的相关gp120蛋白(任何进化枝),或与如本文描述的p24或p26(HIV-2)多肽(亚基)融合的90%、或80%或70%、或60%或50%或最少的已知表位。在一些实施方案中,gp120蛋白可以直接与p24蛋白(或p26)融合,或在其他实施方案中,被如本文描述的融合蛋白(例如Fc、网格蛋白、p53等)与p24蛋白(或p26)间隔。这些蛋白可以用于血浆、血清或全血中抗体的前沿筛选,或用于诊断目的或用于证实性测定。
在一些方面中,实施方案包括多肽,所述多肽包含与100%的相关p24蛋白(或p26)融合的gp120多肽(任何相关进化枝),或与HIV-1或HIV-2的gp120多肽融合的90%、或80%或者70%、或60%或50%或最少的已知表位。在一些实施方案中,gp120蛋白可以直接与p24蛋白融合,或在其他实施方案中,被如本文描述的支架(例如Fc、网格蛋白、p53等)与p24蛋白间隔。这些蛋白可以用于血浆、血清或全血中抗体的前沿筛选,或用于诊断目的或用于证实性测定。
gp120结构域(表位)可以是在其C-末端与寡聚化结构域(例如Fc或本领域技术人员熟悉的如本文下文的其他结构域)融合的在本文中列出的许多中的一个,该寡聚化结构域与p24结构域(或p26)(表位)的N-末端融合。可选择地,p24结构域可以在N-末端处,并且寡聚化结构域与各个gp120蛋白结构域(表位)(SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88或SEQ ID NO:89)的N-末端融合。这些可以是单体的、二聚的、三聚的、或四聚的或五聚的。
在一些方面中,实施方案包括多肽,所述多肽包含与相关p24蛋白(或p26)融合的gp120多肽(或任何相关进化枝),该多肽带有或不带有被设计在p26/26和Fc结构域或其他寡聚化结构域的C末端之间的柔性铰链区。这些蛋白可以用于血浆、血清或全血中的抗体前沿筛选,或用于诊断目的或用于证实性测定。
III.寡聚多肽
在一些方面中,实施方案包括寡聚多肽,所述寡聚多肽包含如本文描述的2种、3种、4种或更多种多肽(亚基)。在一些实施方案中,寡聚多肽是二聚体多肽,即包含两个亚基的寡聚多肽,其中每个亚基是本文描述的多肽。如在没有修饰词“寡聚”、“二聚”或其他明确提及多亚基形式的情况下使用的术语“多肽”指的是单体多肽,其可以存在或可以不存在于寡聚体例如二聚体、三聚体或四聚体中。
寡聚多肽的每个亚基通常具有相同的氨基酸序列,但是寡聚多肽的不同亚基可以具有不同的氨基酸序列。异二聚体多肽可以例如通过以下来制备:用离去基团(例如,用2-2’二硫代-双-(5-硝基吡啶))活化第一亚基的半胱氨酸硫醇,还原第二亚基的硫醇(例如,用β-巯基乙醇或三(2-羧乙基)膦),并且然后使第一亚基和第二亚基接触。可选择地,亚基可以随机交联并且然后纯化。同源二聚体多肽可以使用类似的策略来制备。寡聚多肽可以在寡聚化后纯化,以将期望的寡聚多肽与单体亚基和其他不期望的物质分离。
寡聚多肽可以是对称的,或寡聚多肽可以缺乏对称性。例如,寡聚多肽可以形成“分子间”二硫键模式,导致缺乏对称性的四级结构。
寡聚多肽可以通过非共价或共价相互作用来交联。非共价相互作用的实例是GCN4或网格蛋白寡聚化结构域的三聚化或p53寡聚化结构域的四聚化。共价相互作用的实例是二硫键介导的抗体Fc结构域铰链区的二聚化。具有包含抗体Fc结构域的亚基的二聚体多肽可以通过至少一个二硫键,通常2个二硫键(例如,对于IgG1和IgG4衍生的Fc结构域)或4个二硫键(例如,对于IgG2衍生的Fc结构域)共价交联,但是二硫键的数目没有特别限制。IgG3可以用例如11个二硫键交联。
二聚体多肽可以包含两个亚基,其中每个亚基包含抗体Fc结构域,并且抗体Fc结构域交联二聚体多肽的两个亚基。
三聚体多肽可以包含三个亚基,其中每个亚基包含GCN4三聚化结构域,并且GCN4三聚化结构域非共价地交联三聚体多肽的三个亚基。三聚体多肽可以包含三个亚基,其中每个亚基包含网格蛋白三聚化结构域,并且网格蛋白三聚化结构域非共价地交联三聚体多肽的三个亚基。
四聚体多肽可以包含四个亚基,其中每个亚基包含p53四聚化结构域,并且p53四聚化结构域非共价地交联四聚体多肽的四个亚基。
实施方案还包括包含二聚体多肽的组合物,其中组合物基本上不含不是二聚体多肽的寡聚多肽。组合物可以缺少不是二聚体多肽的寡聚多肽。
多种实施方案还包括包含三聚体多肽的组合物,其中组合物基本上不含不是三聚体多肽的寡聚多肽。组合物可以缺少不是三聚体多肽的寡聚多肽。
多种实施方案还包括包含四聚体多肽的组合物,其中组合物基本上不含不是四聚体多肽的寡聚多肽。组合物可以缺少不是四聚体多肽的寡聚多肽。
在一些实施方案中,组合物包含单体多肽,其中组合物基本上不含寡聚多肽。组合物可以缺少寡聚多肽。
IV.核酸、克隆细胞和表达细胞
本文描述的实施方案还包括包含编码本文描述的多肽的核苷酸序列的核酸。核酸可以是DNA或RNA。包含编码本文描述的多肽的核苷酸序列的DNA通常包含可操作地连接至核苷酸序列的启动子。启动子优选地能够驱动感兴趣的表达细胞中核苷酸序列的组成型或诱导型表达。核酸的精确核苷酸序列没有特别限制,只要核苷酸序列编码本文描述的多肽。密码子可以被选择为,例如匹配感兴趣的表达细胞(例如,哺乳动物细胞诸如人类细胞)的密码子偏好和/或为了克隆期间的方便性。DNA可以是质粒,例如,质粒可以包含复制起点(例如,用于质粒在原核细胞中的复制)。
本公开内容的多个方面还涉及包含核酸的细胞,所述核酸包含编码本文描述的多肽的核苷酸序列。细胞可以是表达细胞或克隆细胞。核酸通常在大肠杆菌中克隆,但是可以使用其他克隆细胞。如果细胞是表达细胞,则核酸任选地是染色体的核酸,即其中核苷酸序列被整合到染色体中,但是核酸也可以例如作为染色体外DNA存在于表达细胞中。
本公开内容的多个方面包括包含核酸的细胞,所述核酸包含编码如本文描述的多肽或寡聚多肽(例如二聚体多肽、三聚体多肽或四聚体多肽)的序列。细胞通常是表达细胞。表达细胞的性质没有特别限制。哺乳动物表达细胞可以允许多肽或寡聚多肽的有利折叠、翻译后修饰和/或分泌,但是其他真核细胞或原核细胞可以用作表达细胞。示例性表达细胞包括CHO、BHK、NS0、Sp2/0、COS、C127、HEK、HT-1080、PER.C6、HeLa和Jurkat细胞。
本发明的表达细胞通常不是酵母,酵母通常用作用于表达重组HIV包膜蛋白的表达细胞。HIV包膜蛋白在酵母中的表达可以导致错误折叠、聚集和/或翻译后异常修饰的累积,这通过在哺乳动物表达细胞(尤其是人类表达细胞)中表达本文描述的多肽来减轻。
V.测定和试剂
实施方案包括免疫测定试剂,所述免疫测定试剂包含如本文描述的多肽或寡聚多肽(例如二聚体多肽),用于测定包含抗HIV抗体的组合物。免疫测定试剂可以被结合至固体支持物。固体支持物可以是例如珠、膜、微量滴定板、多肽芯片或色谱柱的固相。
多种实施方案还包括用于测定包含抗HIV抗体的组合物的装置。装置可以是用于确定样品是否包含抗HIV抗体(例如,用于确定样品是否可以用于输注或移植到人类患者中)的装置。测定是熟知的并且通常以固体支持物为特征,该固体支持物帮助将直接或间接结合固体支持物的组分与不直接或间接结合固体支持物的组分分离。固体支持物可以是例如珠、膜、微量滴定板、多肽芯片或色谱柱的固相。装置可以包含如本文描述的多肽或寡聚多肽(例如二聚体多肽)。多肽或寡聚多肽通常共价地或非共价地结合至固体支持物。
如本文使用的,术语“直接”结合指的是分子与固体支持物的直接缀合,例如将多肽的半胱氨酸硫醇结合至金表面的金-硫醇相互作用。如本文使用的,术语“间接”结合包括多肽与直接结合至表面的另一分子的特异性结合,例如,多肽可以结合直接结合至固体支持物的抗体,从而将多肽间接结合至固体支持物。术语“间接”结合独立于多肽和固体支持物之间的分子的数目,只要分子的雏菊链(daisy chain)之间的每种相互作用是特异性的或是共价相互作用,并且雏菊链的末端分子直接结合至固体支持物。
如本文使用的,术语“非共价结合”指的是例如抗体和其抗原、配体和其受体、或酶和其底物之间的特异性结合,例如通过生物素-链霉亲和素相互作用例示的。特异性结合通常指的是具有小于约100μM,例如小于约10μM、约1μM、约100nM或约10nM的解离常数(KD)的相互作用。还可以设想其中多肽或寡聚多肽从不结合固体支持物的测定,例如竞争性测定。
在示例性测定中,将结合至固体支持物的多肽(或寡聚多肽)与怀疑包含抗HIV抗体的样品,例如血液、血清、血浆、唾液或面颊拭子(cheek swab)样品接触。然后以不显著破坏多肽(或寡聚多肽)和任何抗HIV抗体之间的结合的严格度洗涤(例如磷酸盐缓冲盐水或类似洗涤液)固体支持物。然后将固体支持物与识别HIV抗体的“第二”抗体(例如抗人IgG抗体)接触,其中第二抗体包括检测标记物。检测标记物可以是染料(例如,用于目视检测)、荧光团(例如,用于荧光检测)、酶(例如,辣根过氧化物酶;用于目视检测或荧光检测被放大的信号)、放射性标记或分子生物学或医学诊断中常用的任何其他检测标记物。对该测定的不同改变对于本领域技术人员是容易明显的。例如,样品的抗体可以固定在固体支持物上,多肽(或寡聚多肽)可以与抗体接触,并且然后多肽(或寡聚多肽)可以使用识别多肽(或寡聚多肽)的融合蛋白或亲和标签的抗体或配体来检测。
实施方案还包括测定样品的方法,所述方法包括使如本文描述的多肽或寡聚多肽与样品接触。另外的实施方案包括确定样品是否包含抗HIV抗体的方法,所述方法包括使如本文描述的多肽或寡聚多肽与样品接触。实施方案还包括测定样品的方法,所述方法包括使如本文描述的多肽或寡聚多肽与样品接触,以及确定抗体和多肽或寡聚多肽之间的结合亲和力。样品可以是人类样品,例如从人类获得的体液。样品可以是例如血液、血浆、血清、唾液或面颊拭子。样品可以包括血液、血浆、血清、唾液或面颊细胞。样品可以是精子样品。
VI.药物组合物
本发明的多种实施方案涉及包含本文描述的多肽或本文描述的寡聚多肽的组合物。组合物可以包含药学上可接受的载体和/或药学上可接受的赋形剂。例如,组合物可以是疫苗。
本发明的多种实施方案涉及治疗或预防人类患者中的HIV感染的方法,所述方法包括向患者施用包含如本文描述的多肽或如本文描述的寡聚多肽的组合物。如本文使用的术语“预防(preventing)”指的是预防(prophylaxis),其包括向患者施用组合物以相对于未接受该组合物的其他类似患者降低患者将感染HIV的可能性。术语预防还包括向一组患者施用组合物,以相对于未接受该组合物的其他类似组的患者减少该组中感染HIV的患者的数目。
本发明的多种实施方案涉及治疗或预防人类患者中的HIV感染的方法,所述方法包括向患者施用根据本文描述的实施方案的疫苗。
患者可能感染HIV,患者可能已经暴露于HIV,或者患者可能处于增加的暴露于HIV和/或感染HIV的风险中。
VII.选择抗体的方法
实施方案还包括用于产生抗体的方法,所述方法包括向动物施用本文描述的多肽或寡聚多肽(例如二聚体多肽)。动物可以是例如小鼠、兔、大鼠、仓鼠、豚鼠、山羊、绵羊、马或鸡。
另外的实施方案包括用于测定包含抗体的样品的方法,所述方法包括使样品与本文描述的多肽或寡聚多肽(例如二聚体多肽、三聚体多肽或四聚体多肽)接触,以及确定抗体和多肽或寡聚多肽之间的结合亲和力。结合亲和力可以是相对结合亲和力,例如,结合亲和力可以相对于样品中存在的一种或更多种不同抗体的结合亲和力,或使用基本上相同的方法或以其他方式测定的结合亲和力。类似地,结合亲和力可以是定量性结合亲和力,例如,方法可以包括将解离常数(KD)确定在特定值的期望范围内,例如±一个数量级、50%、10%等。方法可以是抗体亲和力成熟的方法。
实施方案还包括从多种抗体中选择抗HIV抗体的方法。方法可以包括使如本文描述的多肽或寡聚多肽(例如,二聚体多肽)与包含多种抗体的组合物接触,以及鉴定相对于组合物中的其他抗体对多肽或寡聚多肽具有高结合亲和力的抗体,从而选择抗HIV抗体。方法可以是选择抗HIV抗体的方法,该抗HIV抗体特异性结合如本文描述的gp120氨基酸序列或gp41氨基酸序列的抗原决定簇。
VIII.选择生物样品的方法
另外的实施方案还包括从人类生物样品的供应物选择生物样品的方法,所述方法包括从该供应物选择包含与如本文描述的多肽或寡聚多肽(例如,二聚体多肽)形成抗原-抗体复合物的抗体的那些样品。这可用于从供应物中鉴定待被去除的HIV阳性样品,当供应物是血液供应物时这是特别有意义的。那些未被选择的样品可以被采用用于制备血液相关产品。通过鉴定HIV阳性样品,方法还可以用于富集阳性样品。
实施方案还包括从人类生物样品的供应物选择生物样品的方法,所述方法包括从该供应物选择不包含与根据本发明的免疫测定试剂形成抗原-抗体复合物的抗体的那些样品。这可用于鉴定可用于制备血液相关产品的生物样品。
实施例
实施例1.包含HIV包膜蛋白的表位的多肽的设计
设计了包含HIV包膜蛋白的表位的多种多肽。多肽env_1至env_4使用衍生自LANLHIV-1gp160包膜表位图(https://www.hiv.lanl.gov/content/immunology/maps/ab/gp160.html)的gp120人B细胞表位来设计,使用α螺旋或β片层接头序列拼接在一起。还将这些序列与鼠IgG CH2/CH3区域融合。在一些形式中,包括了IgG铰链区,从而允许形成二聚体。多肽env_5使用相同的SYN-gp120序列来设计,与p53的四聚化基序融合。多肽env_6使用SYN-gp120序列来设计,与GCN4的三聚化基序融合。多肽env_7使用SYN-gp120序列来设计,与网格蛋白的三聚化基序融合。多肽env_8和env_9使用来自LANL HIV gp160表位图的对应于gp41的人B细胞表位来设计,用命名为“SYN-gp41”的α螺旋接头拼接在一起,并且与带有或不带有铰链区的IgG CH2/CH3结构域融合。多肽env_10至env_17使用衍生自来自RCSB蛋白数据库(PDB)条目5TE4和5T33的氨基酸序列的HIV-1gp120序列来设计,与带有或不带有铰链区的IgG CH2/CH3结构域或gp120的V3环融合。多肽env_14至env_17还包含衍生自来自RCSB蛋白数据库(PDB)条目5V8L的氨基酸序列的HIV-1gp41序列的一部分,在α螺旋接头之后与IgG CH2/CH3结构域的C-末端融合。多肽env_18和env_19使用衍生自PDB条目5V8L的gp41序列来设计,分别与带有或不带有铰链区的IgG CH2/CH3结构域融合。多肽env_20是具有一个延长的表位区域的多肽env_8的一种修饰形式。多肽env_21与在C-末端处具有融合的SYN-gp120结构域的多肽env_20相同。多肽env_22是衍生自NCBI参考序列NP_579895的截短的gp41序列,并且与SYN-gp120序列融合,在gp41序列和gp120序列之间具有IgG CH2/CH3结构域。多肽env_23和env_24衍生自HIV-1包膜蛋白表位,并且分别在其C-末端或N-末端与IgG CH2/CH3结构域融合。多肽env_25至env_27是对应于HIV包膜蛋白表位的进化枝A、进化枝C和共有序列。多肽env_28和env_29分别对应于在其N-末端或C-末端与IgG CH2/CH3结构域融合的HIV-2包膜蛋白表位。多肽env_30和env_31分别对应于在其N-末端或C-末端与IgGCH2/CH3结构域融合的HIV-1包膜蛋白表位。多肽env_32和env_33对应于多肽env_22中使用的相同的gp41序列,分别具有IgG CH2/CH3结构域融合在其N-末端或C-末端处。多肽env_34对应于衍生自美国专利第6,284,248号的SEQ ID NO:10的gp160序列,该多肽env_34被用作多肽env_35至env_38的对照。该序列不包括包膜跨膜序列,并且具有突变的gp120/gp41裂解位点。多肽env_35至env_38对应于与多肽env_34的序列比对的来自进化枝A、C、AE和共有序列的包膜序列。多肽env_39衍生自HIV-1gp120进化枝B包膜蛋白表位,与衍生自NCBI参考序列NP_579895的截短的gp41序列融合,在gp120序列和gp41序列之间具有IgG CH2/CH3结构域。多肽env_40对应于HIV-1gp120包膜的相同序列、截短的gp41,与IgG CH2/CH3结构域融合在一起但具有更长的接头。多肽env_41对应于衍生自NCBI参考序列NP_579895的截短的gp41序列,在其C-末端与HIV-1gp120包膜蛋白表位融合,在gp41序列和gp120序列之间具有IgG CH2/CH3结构域。多肽env_42至env_44与多肽env_40类似,但分别使用来自进化枝A、AE和AG毒株的gp120序列。多肽env_45与多肽env_40类似,但使用共有的gp120序列。多肽env_46衍生自HIV-1gp120进化枝B包膜蛋白表位,与HIV-1衣壳蛋白p24序列融合,在gp120序列和p24序列之间具有IgG CH2/CH3结构域。多肽env_47衍生自HIV-1衣壳蛋白p24序列,与HIV-1gp120进化枝B包膜蛋白表位融合,在p24序列和gp120序列之间具有IgG CH2/CH3结构域。多肽env_48与多肽env_46类似,其中去除了所选择的p24蛋白的表位。多肽env_49与多肽env_47类似,其中去除了所选择的p24蛋白的表位。多肽env_50与多肽env_46类似,带有对所选择的p24的突变。多肽env_51与多肽env_47类似,带有对所选择的p24的突变。多肽env_52与多肽env_46类似,在p24序列中带有挑选的丙氨酸取代。多肽env_53与多肽env_47类似,在p24序列中带有挑选的丙氨酸取代。多肽env_54对应于HIV-1gp41序列,在其C-末端与带有IgG CH2/CH3结构域的HIV-1gp120蛋白融合。
从env_1至env_38的每个编号的“多肽”对应于SEQ ID NO:1至SEQ ID NO:38。从env_39至env_54的每个编号的“多肽”对应于SEQ ID NO:91至SEQ ID NO:106。
实施例2.env重组多肽的模型
实施例1中描述的并且分别具有SEQ ID NO:1-38和SEQ ID NO:91-106中列出的氨基酸序列的多肽env_1至env_38和env_39至env_54的结构使用Cyrus Biotech蛋白建模工具中的Rosetta软件预测,或通过将来自PDB的已知结构手动拼接在一起使用PyMol来预测。图2-图40和图44是用PyMol呈现的。融合蛋白以深灰色示出,并且HIV包膜蛋白(其包含一个或更多个表位)的氨基酸序列以浅灰色示出。
图2是代表由SEQ ID NO:1和SEQ ID NO:3中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图3是代表由SEQ ID NO:2和SEQ ID NO:4中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图4是代表由SEQ ID NO:5中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图5是代表由SEQ ID NO:6中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图6是代表由SEQ ID NO:7中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图7是代表由SEQ ID NO:8和SEQ ID NO:20中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图8是代表由SEQ ID NO:9中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图9是代表由SEQ ID NO:10、SEQ ID NO:11和SEQ ID NO:12中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图10是代表由SEQ ID NO:13或SEQ ID NO:15中列出的氨基酸序列编码的两种单体多肽形成的二聚体多肽的二聚体多肽的模型。
图11是代表由SEQ ID NO:14和SEQ ID NO:16中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图12是代表由SEQ ID NO:15或SEQ ID NO:17中列出的氨基酸序列编码的两种单体多肽形成的二聚体多肽的二聚体多肽的模型。
图13是代表由SEQ ID NO:18中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图14是代表由SEQ ID NO:19中列出的氨基酸序列编码的两种单体多肽形成的二聚体多肽的二聚体多肽的模型。
图15是代表由SEQ ID NO:21中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图16是代表由SEQ ID NO:22中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图17是代表由SEQ ID NO:23中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图18是代表由SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26和SEQ ID NO:27中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图19是代表由SEQ ID NO:28中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图20是代表由SEQ ID NO:29中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图21是代表由SEQ ID NO:30中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图22是代表由SEQ ID NO:31中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图23是代表由SEQ ID NO:32中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图24是代表由SEQ ID NO:33中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图25是代表由SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37和SEQID NO:38中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图26是代表由SEQ ID NO:92中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图27是代表由SEQ ID NO:93中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图28是代表由SEQ ID NO:94中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图29是代表由SEQ ID NO:95中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图30是代表由SEQ ID NO:96中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图31是代表由SEQ ID NO:97中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图32是代表由SEQ ID NO:98中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图33是代表由SEQ ID NO:99中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图34是代表由SEQ ID NO:100中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图35是代表由SEQ ID NO:101中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图36是代表由SEQ ID NO:102中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图37是代表由SEQ ID NO:103中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图38是代表由SEQ ID NO:104中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图39是代表由SEQ ID NO:105中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图40是代表由SEQ ID NO:106中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
图44是代表由SEQ ID NO:91中列出的氨基酸序列编码的单体亚基的单体多肽的模型。
实施例3.重组多肽的克隆和表达
将多肽env_1、env_2、env_3、env_4、env_5、env_8、env_9、env_10、env_11、env_12、env_13、env_14、env_15、env_16、env_17和env_18克隆、在哺乳动物细胞中表达,并且分离细胞上清液。在于还原和非还原条件下运行的4%-20%tris-甘氨酸TGXTM十二烷基硫酸钠聚丙烯酰胺(SDS-PAGE)凝胶上分析来自细胞上清液的蛋白质。将凝胶用InstantBlueTM蛋白染色剂染色。多肽env_1、env_2、env_3、env_5、env_8、env_9、env_10、env_11、env_12、env_13、env_14、env_15、env_16、env_17和env_18以可检测的水平表达(图41和图42)。
实施例4.通过ELISA,哺乳动物表达的重组多肽能够检测供体样品中的HIV抗体
酶联免疫吸附测定(ELISA)用于确定哺乳动物表达的HIV env重组多肽能够检测来自供体的血浆样品中的HIV抗体,所述HIV抗体被酵母表达的HIV抗原Env13(对照)略去。
简言之,将多孔板的孔在室温用相同摩尔浓度的50μl的每种抗原(包括对照抗原Env13(酵母))包被过夜。孵育后,将板用340μl的洗涤缓冲液洗涤两次,并且然后在室温用封闭缓冲液封闭90分钟。在封闭板后,将封闭缓冲液从孔中抽吸出来,并且将5μl的每种供体样品与50μl的样品稀释剂一起加入到孔中。然后将板覆盖并在37℃孵育45min。此后,将板用340μl的1x洗涤缓冲液洗涤4次,并且将50μl的抗IgG-HRP缀合物加入到每个孔中。将板覆盖并在37℃再次孵育45min,并且用340μl的1x洗涤缓冲液再次洗涤。底物溶液通过每12ml溶解一个OPD的片剂(20mg)的底物缓冲液来制备。稍后向每个孔加入50μl的底物溶液,并且将板在室温在黑暗中再孵育30min。最后,向每个孔加入15μl的4N H2SO4以停止反应。结合的抗原通过在490nm处通过吸收光谱法监测辣根过氧化物酶底物向产物的转化来定量。测试了最多337个样品。
对照抗原Env13(酵母)仅在测试的337个样品中的307个样品中检测到阳性击中(positive hit)。测试的大多数哺乳动物衍生的env抗原能够检测被Env13漏掉的阳性击中。被Env13(酵母)漏掉的所有样品似乎是低滴度样品。然而,哺乳动物衍生的env多肽能够覆盖被Env13(酵母表达)漏掉的多达4个样品。表1的结果证明,哺乳动物衍生的新的env重组多肽允许检测供体样品中被现有技术抗原Env13(酵母)漏掉的HIV抗体。
表1.通过HIV env重组多肽检测供体样品中的HIV抗体
序列表
<110> 盖立复诊断解决方案公司
<120> 哺乳动物表达的新型人类免疫缺陷病毒包膜蛋白抗原
<130> 62588085
<150> US 62/588,085
<151> 2017-11-17
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Arg Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe Val Thr
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Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Phe Gly Asn
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Asn Lys Thr Ile Ile Phe Lys Gln Ser Ser Gly Gly Asp Ala Glu Ala
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Ala Ala Lys Glu Ala Ala Ala Lys Ala Ala Glu Ala Ala Ala Lys Glu
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Ala Ala Ala Lys Ala Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp
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Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile
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Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Leu Thr Arg Asp
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Gly Gly Asn Ser Asn Asn Glu Ser Glu Ile Phe Arg Pro Gly Gly Gly
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Asp Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Ile Glu Pro
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Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
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Lys Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
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Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys
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Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp
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Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln
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Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly
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Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu
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Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe
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Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr
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Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys
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Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys Ile Tyr
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Thr Ser Cys Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn
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Gly Pro Cys Thr Asn Val Ser Thr Val Thr Trp Ile Gln Asn Pro Gly
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Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys Ile Tyr Thr Cys Thr Arg
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Pro Asn Asn Asn Thr Arg Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly
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Arg Ala Phe Val Thr Ile Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp
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Tyr Gln Asn Pro Gly Thr Lys Ile Tyr Thr Phe Gly Asn Asn Lys Thr
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Ile Ile Phe Lys Gln Ser Ser Gly Gly Asp Thr Trp Ile Gln Asn Pro
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Gly Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys Ile Tyr Thr Pro Cys
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Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly Lys Ala Met
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Tyr Ala Pro Pro Ile Ser Gly Gln Ile Ala Glu Ala Ala Ala Lys Glu
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Ala Ala Ala Lys Ala Leu Thr Arg Asp Gly Gly Asn Ser Asn Asn Glu
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Ser Glu Ile Phe Arg Pro Gly Gly Gly Asp Ala Glu Ala Ala Ala Lys
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Glu Ala Ala Ala Lys Ala Ile Glu Pro Leu Gly Val Ala Pro Thr Lys
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Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg Gly Gly Gly Pro Ser
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Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile
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Ser Leu Trp Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe
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Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val
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Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile
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Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr
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His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro
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Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val
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Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro
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Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu
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Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp
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Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr
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Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser
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Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu
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Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His
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His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys
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Asp Thr Thr Ser Tyr Lys Leu Thr Ser Cys Ala Glu Ala Ala Ala Lys
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Arg Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe Val Thr
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Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Phe Gly Asn
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Asn Lys Thr Ile Ile Phe Lys Gln Ser Ser Gly Gly Asp Ala Glu Ala
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Ala Ala Ala Lys Ala Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp
225 230 235 240
Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile
245 250 255
Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Leu Thr Arg Asp
260 265 270
Gly Gly Asn Ser Asn Asn Glu Ser Glu Ile Phe Arg Pro Gly Gly Gly
275 280 285
Asp Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Ile Glu Pro
290 295 300
Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
305 310 315 320
Lys Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys
325 330 335
Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val
340 345 350
Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp
355 360 365
Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe
370 375 380
Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp
385 390 395 400
Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe
405 410 415
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys
420 425 430
Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys
435 440 445
Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp
450 455 460
Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys
465 470 475 480
Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser
485 490 495
Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr
500 505 510
Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser
515 520 525
Leu Ser His Ser Pro Gly Ile
530 535
<210> 4
<211> 606
<212> PRT
<213> 合成的
<400> 4
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln
20 25 30
Asn Pro Gly Thr Lys Ile Tyr Thr Cys Thr Asp Leu Lys Asn Asp Thr
35 40 45
Asn Thr Asn Ser Ser Ser Gly Arg Met Ile Met Glu Lys Thr Trp Ile
50 55 60
Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys Ile Tyr
65 70 75 80
Thr Thr Ser Ile Arg Gly Lys Val Gln Lys Glu Tyr Ala Phe Phe Tyr
85 90 95
Lys Leu Asp Ile Ile Pro Ile Asp Asn Asp Thr Thr Ser Tyr Lys Leu
100 105 110
Thr Ser Cys Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn
115 120 125
Pro Gly Thr Lys Ile Tyr Thr Pro Ile Pro Ile His Tyr Cys Ala Pro
130 135 140
Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr
145 150 155 160
Gly Pro Cys Thr Asn Val Ser Thr Val Thr Trp Ile Gln Asn Pro Gly
165 170 175
Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys Ile Tyr Thr Cys Thr Arg
180 185 190
Pro Asn Asn Asn Thr Arg Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly
195 200 205
Arg Ala Phe Val Thr Ile Thr Trp Ile Gln Asn Pro Gly Thr Lys Ile
210 215 220
Tyr Thr Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys Gln Ser Ser Gly
225 230 235 240
Gly Asp Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn Pro
245 250 255
Gly Thr Lys Ile Tyr Thr Pro Cys Arg Ile Lys Gln Ile Ile Asn Met
260 265 270
Trp Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln
275 280 285
Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Leu Thr Arg
290 295 300
Asp Gly Gly Asn Ser Asn Asn Glu Ser Glu Ile Phe Arg Pro Gly Gly
305 310 315 320
Gly Asp Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Ile Glu
325 330 335
Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg
340 345 350
Glu Lys Arg Gly Gly Gly Pro Ser Asn Met Trp Lys Asn Asp Met Val
355 360 365
Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Val Pro Arg Asp Cys
370 375 380
Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe
385 390 395 400
Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro
405 410 415
Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val
420 425 430
Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr
435 440 445
Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu
450 455 460
Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys
465 470 475 480
Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser
485 490 495
Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro
500 505 510
Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile
515 520 525
Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly
530 535 540
Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp
545 550 555 560
Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp
565 570 575
Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His
580 585 590
Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Ile
595 600 605
<210> 5
<211> 378
<212> PRT
<213> 合成的
<400> 5
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His
20 25 30
Glu Asp Ile Ile Ser Leu Trp Cys Thr Asp Leu Lys Asn Asp Thr Asn
35 40 45
Thr Asn Ser Ser Ser Gly Arg Met Ile Met Glu Lys Ala Glu Ala Ala
50 55 60
Ala Lys Glu Ala Ala Ala Lys Ala Thr Ser Ile Arg Gly Lys Val Gln
65 70 75 80
Lys Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile Ile Pro Ile Asp Asn
85 90 95
Asp Thr Thr Ser Tyr Lys Leu Thr Ser Cys Ala Glu Ala Ala Ala Lys
100 105 110
Glu Ala Ala Ala Lys Ala Pro Ile Pro Ile His Tyr Cys Ala Pro Ala
115 120 125
Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly
130 135 140
Pro Cys Thr Asn Val Ser Thr Val Cys Thr Arg Pro Asn Asn Asn Thr
145 150 155 160
Arg Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe Val Thr
165 170 175
Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Phe Gly Asn
180 185 190
Asn Lys Thr Ile Ile Phe Lys Gln Ser Ser Gly Gly Asp Ala Glu Ala
195 200 205
Ala Ala Lys Glu Ala Ala Ala Lys Ala Ala Glu Ala Ala Ala Lys Glu
210 215 220
Ala Ala Ala Lys Ala Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp
225 230 235 240
Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile
245 250 255
Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Leu Thr Arg Asp
260 265 270
Gly Gly Asn Ser Asn Asn Glu Ser Glu Ile Phe Arg Pro Gly Gly Gly
275 280 285
Asp Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Ile Glu Pro
290 295 300
Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
305 310 315 320
Lys Gly Gly Gly Pro Ser Gly Gly Gly Pro Ser Lys Pro Leu Asp Gly
325 330 335
Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu Arg Phe Glu Met Phe
340 345 350
Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp Ala Gln Ala Gly Lys
355 360 365
Glu Pro Gly His His His His His His His
370 375
<210> 6
<211> 405
<212> PRT
<213> 合成的
<400> 6
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Cys Thr Asp Leu Lys Asn Asp Thr Asn Thr Asn Ser
20 25 30
Ser Ser Gly Arg Met Ile Met Glu Lys Thr Trp Ile Gln Asn Pro Gly
35 40 45
Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys Ile Tyr Thr Thr Ser Ile
50 55 60
Arg Gly Lys Val Gln Lys Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile
65 70 75 80
Ile Pro Ile Asp Asn Asp Thr Thr Ser Tyr Lys Leu Thr Ser Cys Thr
85 90 95
Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys
100 105 110
Ile Tyr Thr Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Thr
130 135 140
Asn Val Ser Thr Val Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr
145 150 155 160
Gln Asn Pro Gly Thr Lys Ile Tyr Thr Cys Thr Arg Pro Asn Asn Asn
165 170 175
Thr Arg Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe Val
180 185 190
Thr Ile Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn Pro
195 200 205
Gly Thr Lys Ile Tyr Thr Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys
210 215 220
Gln Ser Ser Gly Gly Asp Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp
225 230 235 240
Tyr Gln Asn Pro Gly Thr Lys Ile Tyr Thr Pro Cys Arg Ile Lys Gln
245 250 255
Ile Ile Asn Met Trp Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro
260 265 270
Ile Ser Gly Gln Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys
275 280 285
Ala Leu Thr Arg Asp Gly Gly Asn Ser Asn Asn Glu Ser Glu Ile Phe
290 295 300
Arg Pro Gly Gly Gly Asp Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala
305 310 315 320
Lys Ala Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg
325 330 335
Val Val Gln Arg Glu Lys Arg Gly Gly Gly Pro Ser Asn Met Trp Lys
340 345 350
Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Gly
355 360 365
Gly Gly Pro Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala
370 375 380
Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu His
385 390 395 400
His His His His His
405
<210> 7
<211> 477
<212> PRT
<213> 合成的
<400> 7
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Cys Thr Asp Leu Lys Asn Asp Thr Asn Thr Asn Ser
20 25 30
Ser Ser Gly Arg Met Ile Met Glu Lys Thr Trp Ile Gln Asn Pro Gly
35 40 45
Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys Ile Tyr Thr Thr Ser Ile
50 55 60
Arg Gly Lys Val Gln Lys Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile
65 70 75 80
Ile Pro Ile Asp Asn Asp Thr Thr Ser Tyr Lys Leu Thr Ser Cys Thr
85 90 95
Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn Pro Gly Thr Lys
100 105 110
Ile Tyr Thr Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Thr
130 135 140
Asn Val Ser Thr Val Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr
145 150 155 160
Gln Asn Pro Gly Thr Lys Ile Tyr Thr Cys Thr Arg Pro Asn Asn Asn
165 170 175
Thr Arg Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe Val
180 185 190
Thr Ile Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn Pro
195 200 205
Gly Thr Lys Ile Tyr Thr Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys
210 215 220
Gln Ser Ser Gly Gly Asp Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp
225 230 235 240
Tyr Gln Asn Pro Gly Thr Lys Ile Tyr Thr Pro Cys Arg Ile Lys Gln
245 250 255
Ile Ile Asn Met Trp Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro
260 265 270
Ile Ser Gly Gln Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys
275 280 285
Ala Leu Thr Arg Asp Gly Gly Asn Ser Asn Asn Glu Ser Glu Ile Phe
290 295 300
Arg Pro Gly Gly Gly Asp Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala
305 310 315 320
Lys Ala Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg
325 330 335
Val Val Gln Arg Glu Lys Arg Gly Gly Gly Pro Ser Asn Met Trp Lys
340 345 350
Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Gly
355 360 365
Gly Gly Pro Ser Gly Gly Gly Pro Ser Gly Ser His Met Trp Lys Gln
370 375 380
Ser Val Glu Leu Ala Lys Lys Asp Ser Leu Tyr Lys Asp Ala Met Gln
385 390 395 400
Tyr Ala Ser Glu Ser Lys Asp Thr Glu Leu Ala Glu Glu Leu Leu Gln
405 410 415
Trp Phe Leu Gln Glu Glu Lys Arg Glu Cys Phe Gly Ala Cys Leu Phe
420 425 430
Thr Cys Tyr Asp Leu Leu Arg Pro Asp Val Val Leu Glu Leu Ala Trp
435 440 445
Arg His Asn Ile Met Asp Phe Ala Met Pro Tyr Phe Ile Gln Val Met
450 455 460
Lys Glu Tyr Leu Thr Lys Val His His His His His His
465 470 475
<210> 8
<211> 526
<212> PRT
<213> 合成的
<400> 8
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Val Gly Ile Ala Val Gly Ile Ala Glu Ala Ala
20 25 30
Ala Lys Glu Ala Ala Ala Lys Ala Gly Ala Leu Phe Leu Gly Phe Leu
35 40 45
Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val
50 55 60
Gln Ala Arg Gln Leu Leu Ser Ala Glu Ala Ala Ala Lys Glu Ala Ala
65 70 75 80
Ala Lys Ala Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly
85 90 95
Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys
100 105 110
Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys
115 120 125
Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Ala Glu Ala Ala Ala
130 135 140
Lys Glu Ala Ala Ala Lys Ala Thr Ser Leu Ile His Ser Leu Ile Glu
145 150 155 160
Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu
165 170 175
Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu
180 185 190
Trp Tyr Ile Lys Leu Phe Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala
195 200 205
Ala Lys Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu
210 215 220
Gly Gly Glu Arg Asp Arg Asp Arg Ser Ile Ala Glu Ala Ala Ala Lys
225 230 235 240
Glu Ala Ala Ala Lys Ala Tyr His Arg Leu Arg Asp Leu Leu Leu Ile
245 250 255
Val Thr Arg Ile Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Glu
260 265 270
Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Gly Thr Asp Arg Val Ile
275 280 285
Glu Val Val Gln Gly Ala Cys Arg Ala Ile Arg His Ile Pro Arg Arg
290 295 300
Ile Arg Gln Gly Leu Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe
305 310 315 320
Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro
325 330 335
Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val
340 345 350
Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr
355 360 365
Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala
370 375 380
Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys
385 390 395 400
Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser
405 410 415
Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro
420 425 430
Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val
435 440 445
Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly
450 455 460
Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp
465 470 475 480
Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp
485 490 495
Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His
500 505 510
Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys
515 520 525
<210> 9
<211> 523
<212> PRT
<213> 合成的
<400> 9
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Val Gly Ile Ala Val Gly Ile Ala Glu Ala Ala
20 25 30
Ala Lys Glu Ala Ala Ala Lys Ala Gly Ala Leu Phe Leu Gly Phe Leu
35 40 45
Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val
50 55 60
Gln Ala Arg Gln Leu Leu Ser Ala Glu Ala Ala Ala Lys Glu Ala Ala
65 70 75 80
Ala Lys Ala Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly
85 90 95
Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys
100 105 110
Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys
115 120 125
Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Ala Glu Ala Ala Ala
130 135 140
Lys Glu Ala Ala Ala Lys Ala Thr Ser Leu Ile His Ser Leu Ile Glu
145 150 155 160
Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu
165 170 175
Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu
180 185 190
Trp Tyr Ile Lys Leu Phe Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala
195 200 205
Ala Lys Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu
210 215 220
Gly Gly Glu Arg Asp Arg Asp Arg Ser Ile Ala Glu Ala Ala Ala Lys
225 230 235 240
Glu Ala Ala Ala Lys Ala Tyr His Arg Leu Arg Asp Leu Leu Leu Ile
245 250 255
Val Thr Arg Ile Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Glu
260 265 270
Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Gly Thr Asp Arg Val Ile
275 280 285
Glu Val Val Gln Gly Ala Cys Arg Ala Ile Arg His Ile Pro Arg Arg
290 295 300
Ile Arg Gln Gly Leu Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
305 310 315 320
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
325 330 335
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
340 345 350
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
355 360 365
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
370 375 380
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
385 390 395 400
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
405 410 415
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
420 425 430
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
435 440 445
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
450 455 460
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
465 470 475 480
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
485 490 495
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
500 505 510
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Ile
515 520
<210> 10
<211> 624
<212> PRT
<213> 合成的
<400> 10
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Cys Ile Arg Pro Asn Asn Gly Gly Ser
195 200 205
Gly Ser Gly Gly Asp Ile Arg Gln Ala His Cys Asn Val Thr Arg Ser
210 215 220
Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu Trp Lys Ile
225 230 235 240
Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile Phe Asn Ser
245 250 255
Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Gly
260 265 270
Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn Glu Thr Asn
275 280 285
Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr Leu Gln Cys
290 295 300
Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly Gln Ala Met
305 310 315 320
Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser Asn Ile Thr
325 330 335
Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His Asp Lys Glu
340 345 350
Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp Asn Trp Arg
355 360 365
Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile Asn Phe Ala
370 375 380
Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Ala
385 390 395 400
Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile
405 410 415
Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val
420 425 430
Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val
435 440 445
Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp
450 455 460
Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln
465 470 475 480
Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp
485 490 495
Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val
500 505 510
Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr
515 520 525
Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu
530 535 540
Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr
545 550 555 560
Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr
565 570 575
Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr
580 585 590
Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr Lys
595 600 605
Ser Phe Ser Arg Thr Pro Gly Lys His His His His His His His His
610 615 620
<210> 11
<211> 639
<212> PRT
<213> 合成的
<400> 11
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Cys Ile Arg Pro Asn Asn Gly Gly Ser
195 200 205
Gly Ser Gly Gly Asp Ile Arg Gln Ala His Cys Asn Val Thr Arg Ser
210 215 220
Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu Trp Lys Ile
225 230 235 240
Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile Phe Asn Ser
245 250 255
Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Gly
260 265 270
Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn Glu Thr Asn
275 280 285
Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr Leu Gln Cys
290 295 300
Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly Gln Ala Met
305 310 315 320
Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser Asn Ile Thr
325 330 335
Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His Asp Lys Glu
340 345 350
Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp Asn Trp Arg
355 360 365
Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile Asn Phe Ala
370 375 380
Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Pro
385 390 395 400
Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro
405 410 415
Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys
420 425 430
Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val
435 440 445
Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn
450 455 460
Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr
465 470 475 480
Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp
485 490 495
Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu
500 505 510
Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg
515 520 525
Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys
530 535 540
Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp
545 550 555 560
Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys
565 570 575
Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser
580 585 590
Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser
595 600 605
Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser
610 615 620
Phe Ser Arg Thr Pro Gly Lys His His His His His His His His
625 630 635
<210> 12
<211> 611
<212> PRT
<213> 合成的
<400> 12
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Asp Ile Arg Gln Ala His Cys Asn Val
195 200 205
Thr Arg Ser Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu
210 215 220
Trp Lys Ile Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile
225 230 235 240
Phe Asn Ser Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe
245 250 255
Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn
260 265 270
Glu Thr Asn Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr
275 280 285
Leu Gln Cys Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly
290 295 300
Gln Ala Met Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser
305 310 315 320
Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His
325 330 335
Asp Lys Glu Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp
340 345 350
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile
355 360 365
Asn Phe Ala Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser
370 375 380
Phe Asn Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro
385 390 395 400
Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr
405 410 415
Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser
420 425 430
Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His
435 440 445
Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile
450 455 460
Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn
465 470 475 480
Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys
485 490 495
Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu
500 505 510
Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe
515 520 525
Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu
530 535 540
Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr
545 550 555 560
Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg
565 570 575
Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His
580 585 590
Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys His His His His His
595 600 605
His His His
610
<210> 13
<211> 626
<212> PRT
<213> 合成的
<400> 13
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Asp Ile Arg Gln Ala His Cys Asn Val
195 200 205
Thr Arg Ser Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu
210 215 220
Trp Lys Ile Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile
225 230 235 240
Phe Asn Ser Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe
245 250 255
Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn
260 265 270
Glu Thr Asn Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr
275 280 285
Leu Gln Cys Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly
290 295 300
Gln Ala Met Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser
305 310 315 320
Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His
325 330 335
Asp Lys Glu Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp
340 345 350
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile
355 360 365
Asn Phe Ala Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser
370 375 380
Phe Asn Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys
385 390 395 400
Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
405 410 415
Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys
420 425 430
Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp
435 440 445
Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg
450 455 460
Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln
465 470 475 480
His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn
485 490 495
Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly
500 505 510
Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu
515 520 525
Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met
530 535 540
Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu
545 550 555 560
Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe
565 570 575
Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn
580 585 590
Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr
595 600 605
Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys His His His His His His
610 615 620
His His
625
<210> 14
<211> 800
<212> PRT
<213> 合成的
<400> 14
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Cys Ile Arg Pro Asn Asn Gly Gly Ser
195 200 205
Gly Ser Gly Gly Asp Ile Arg Gln Ala His Cys Asn Val Thr Arg Ser
210 215 220
Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu Trp Lys Ile
225 230 235 240
Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile Phe Asn Ser
245 250 255
Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Gly
260 265 270
Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn Glu Thr Asn
275 280 285
Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr Leu Gln Cys
290 295 300
Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly Gln Ala Met
305 310 315 320
Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser Asn Ile Thr
325 330 335
Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His Asp Lys Glu
340 345 350
Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp Asn Trp Arg
355 360 365
Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile Asn Phe Ala
370 375 380
Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Ala
385 390 395 400
Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile
405 410 415
Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val
420 425 430
Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val
435 440 445
Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp
450 455 460
Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln
465 470 475 480
Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp
485 490 495
Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val
500 505 510
Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr
515 520 525
Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu
530 535 540
Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr
545 550 555 560
Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr
565 570 575
Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr
580 585 590
Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr Lys
595 600 605
Ser Phe Ser Arg Thr Pro Gly Lys Ala Glu Ala Ala Ala Lys Glu Ala
610 615 620
Ala Ala Lys Ala Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu
625 630 635 640
Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val
645 650 655
Gln Ala Arg Asn Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu
660 665 670
Leu Arg Ala Pro Glu Ala Gln Gln His Leu Leu Lys Leu Thr Val Trp
675 680 685
Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu
690 695 700
Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile
705 710 715 720
Cys Cys Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Arg Asn Leu
725 730 735
Ser Glu Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys Glu Ile
740 745 750
Ser Asn Tyr Thr Gln Ile Ile Tyr Gly Leu Leu Glu Glu Ser Gln Asn
755 760 765
Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys Trp Ala
770 775 780
Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile Gln
785 790 795 800
<210> 15
<211> 815
<212> PRT
<213> 合成的
<400> 15
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Cys Ile Arg Pro Asn Asn Gly Gly Ser
195 200 205
Gly Ser Gly Gly Asp Ile Arg Gln Ala His Cys Asn Val Thr Arg Ser
210 215 220
Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu Trp Lys Ile
225 230 235 240
Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile Phe Asn Ser
245 250 255
Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Gly
260 265 270
Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn Glu Thr Asn
275 280 285
Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr Leu Gln Cys
290 295 300
Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly Gln Ala Met
305 310 315 320
Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser Asn Ile Thr
325 330 335
Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His Asp Lys Glu
340 345 350
Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp Asn Trp Arg
355 360 365
Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile Asn Phe Ala
370 375 380
Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Pro
385 390 395 400
Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro
405 410 415
Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys
420 425 430
Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val
435 440 445
Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn
450 455 460
Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr
465 470 475 480
Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp
485 490 495
Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu
500 505 510
Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg
515 520 525
Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys
530 535 540
Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp
545 550 555 560
Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys
565 570 575
Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser
580 585 590
Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser
595 600 605
Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser
610 615 620
Phe Ser Arg Thr Pro Gly Lys Ala Glu Ala Ala Ala Lys Glu Ala Ala
625 630 635 640
Ala Lys Ala Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu Gly
645 650 655
Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val Gln
660 665 670
Ala Arg Asn Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu
675 680 685
Arg Ala Pro Glu Ala Gln Gln His Leu Leu Lys Leu Thr Val Trp Gly
690 695 700
Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Arg
705 710 715 720
Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys
725 730 735
Cys Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Arg Asn Leu Ser
740 745 750
Glu Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys Glu Ile Ser
755 760 765
Asn Tyr Thr Gln Ile Ile Tyr Gly Leu Leu Glu Glu Ser Gln Asn Gln
770 775 780
Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys Trp Ala Ser
785 790 795 800
Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile Gln
805 810 815
<210> 16
<211> 787
<212> PRT
<213> 合成的
<400> 16
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Asp Ile Arg Gln Ala His Cys Asn Val
195 200 205
Thr Arg Ser Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu
210 215 220
Trp Lys Ile Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile
225 230 235 240
Phe Asn Ser Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe
245 250 255
Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn
260 265 270
Glu Thr Asn Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr
275 280 285
Leu Gln Cys Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly
290 295 300
Gln Ala Met Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser
305 310 315 320
Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His
325 330 335
Asp Lys Glu Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp
340 345 350
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile
355 360 365
Asn Phe Ala Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser
370 375 380
Phe Asn Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro
385 390 395 400
Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr
405 410 415
Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser
420 425 430
Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His
435 440 445
Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile
450 455 460
Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn
465 470 475 480
Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys
485 490 495
Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu
500 505 510
Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe
515 520 525
Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu
530 535 540
Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr
545 550 555 560
Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg
565 570 575
Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His
580 585 590
Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys Ala Glu Ala Ala Ala
595 600 605
Lys Glu Ala Ala Ala Lys Ala Ala Val Gly Ile Gly Ala Val Phe Leu
610 615 620
Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr
625 630 635 640
Leu Thr Val Gln Ala Arg Asn Leu Leu Ser Gly Ile Val Gln Gln Gln
645 650 655
Ser Asn Leu Leu Arg Ala Pro Glu Ala Gln Gln His Leu Leu Lys Leu
660 665 670
Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu
675 680 685
Arg Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly
690 695 700
Lys Leu Ile Cys Cys Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn
705 710 715 720
Arg Asn Leu Ser Glu Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp
725 730 735
Lys Glu Ile Ser Asn Tyr Thr Gln Ile Ile Tyr Gly Leu Leu Glu Glu
740 745 750
Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp
755 760 765
Lys Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp
770 775 780
Tyr Ile Gln
785
<210> 17
<211> 802
<212> PRT
<213> 合成的
<400> 17
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Asp Ile Arg Gln Ala His Cys Asn Val
195 200 205
Thr Arg Ser Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu
210 215 220
Trp Lys Ile Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile
225 230 235 240
Phe Asn Ser Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe
245 250 255
Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn
260 265 270
Glu Thr Asn Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr
275 280 285
Leu Gln Cys Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly
290 295 300
Gln Ala Met Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser
305 310 315 320
Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His
325 330 335
Asp Lys Glu Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp
340 345 350
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile
355 360 365
Asn Phe Ala Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser
370 375 380
Phe Asn Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys
385 390 395 400
Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
405 410 415
Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys
420 425 430
Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp
435 440 445
Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg
450 455 460
Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln
465 470 475 480
His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn
485 490 495
Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly
500 505 510
Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu
515 520 525
Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met
530 535 540
Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu
545 550 555 560
Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe
565 570 575
Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn
580 585 590
Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr
595 600 605
Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys Ala Glu Ala Ala Ala Lys
610 615 620
Glu Ala Ala Ala Lys Ala Ala Val Gly Ile Gly Ala Val Phe Leu Gly
625 630 635 640
Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu
645 650 655
Thr Val Gln Ala Arg Asn Leu Leu Ser Gly Ile Val Gln Gln Gln Ser
660 665 670
Asn Leu Leu Arg Ala Pro Glu Ala Gln Gln His Leu Leu Lys Leu Thr
675 680 685
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
690 695 700
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
705 710 715 720
Leu Ile Cys Cys Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Arg
725 730 735
Asn Leu Ser Glu Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys
740 745 750
Glu Ile Ser Asn Tyr Thr Gln Ile Ile Tyr Gly Leu Leu Glu Glu Ser
755 760 765
Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys
770 775 780
Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr
785 790 795 800
Ile Gln
<210> 18
<211> 802
<212> PRT
<213> 合成的
<400> 18
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys Ala
20 25 30
Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala Thr
35 40 45
His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu Glu
50 55 60
Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln
65 70 75 80
Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys
85 90 95
Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys Val
100 105 110
Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala
115 120 125
Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys Lys
130 135 140
Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
145 150 155 160
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val Ile
165 170 175
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln Leu
180 185 190
Asn Glu Pro Val Gln Ile Val Asp Ile Arg Gln Ala His Cys Asn Val
195 200 205
Thr Arg Ser Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu
210 215 220
Trp Lys Ile Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile
225 230 235 240
Phe Asn Ser Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe
245 250 255
Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn
260 265 270
Glu Thr Asn Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr
275 280 285
Leu Gln Cys Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly
290 295 300
Gln Ala Met Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser
305 310 315 320
Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His
325 330 335
Asp Lys Glu Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp
340 345 350
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile
355 360 365
Asn Phe Ala Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser
370 375 380
Phe Asn Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys
385 390 395 400
Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
405 410 415
Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys
420 425 430
Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp
435 440 445
Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg
450 455 460
Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln
465 470 475 480
His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn
485 490 495
Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly
500 505 510
Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu
515 520 525
Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met
530 535 540
Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu
545 550 555 560
Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe
565 570 575
Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn
580 585 590
Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr
595 600 605
Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys Ala Glu Ala Ala Ala Lys
610 615 620
Glu Ala Ala Ala Lys Ala Ala Val Gly Ile Gly Ala Val Phe Leu Gly
625 630 635 640
Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu
645 650 655
Thr Val Gln Ala Arg Asn Leu Leu Ser Gly Ile Val Gln Gln Gln Ser
660 665 670
Asn Leu Leu Arg Ala Pro Glu Ala Gln Gln His Leu Leu Lys Leu Thr
675 680 685
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
690 695 700
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
705 710 715 720
Leu Ile Cys Cys Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Arg
725 730 735
Asn Leu Ser Glu Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys
740 745 750
Glu Ile Ser Asn Tyr Thr Gln Ile Ile Tyr Gly Leu Leu Glu Glu Ser
755 760 765
Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys
770 775 780
Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr
785 790 795 800
Ile Gln
<210> 19
<211> 436
<212> PRT
<213> 合成的
<400> 19
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys
20 25 30
Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe
35 40 45
Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val
50 55 60
Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile
65 70 75 80
Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr
85 90 95
His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro
100 105 110
Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val
115 120 125
Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro
130 135 140
Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu
145 150 155 160
Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp
165 170 175
Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr
180 185 190
Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser
195 200 205
Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu
210 215 220
Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His
225 230 235 240
His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys Ala Glu Ala Ala
245 250 255
Ala Lys Glu Ala Ala Ala Lys Ala Ala Val Gly Ile Gly Ala Val Phe
260 265 270
Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met
275 280 285
Thr Leu Thr Val Gln Ala Arg Asn Leu Leu Ser Gly Ile Val Gln Gln
290 295 300
Gln Ser Asn Leu Leu Arg Ala Pro Glu Ala Gln Gln His Leu Leu Lys
305 310 315 320
Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val
325 330 335
Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser
340 345 350
Gly Lys Leu Ile Cys Cys Thr Asn Val Pro Trp Asn Ser Ser Trp Ser
355 360 365
Asn Arg Asn Leu Ser Glu Ile Trp Asp Asn Met Thr Trp Leu Gln Trp
370 375 380
Asp Lys Glu Ile Ser Asn Tyr Thr Gln Ile Ile Tyr Gly Leu Leu Glu
385 390 395 400
Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu
405 410 415
Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu
420 425 430
Trp Tyr Ile Gln
435
<210> 20
<211> 522
<212> PRT
<213> 合成的
<400> 20
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Val Gly Ile Gly Ala Leu Phe Leu Gly Phe Leu
20 25 30
Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val
35 40 45
Gln Ala Arg Gln Leu Leu Ser Ala Glu Ala Ala Ala Lys Glu Ala Ala
50 55 60
Ala Lys Ala Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly
65 70 75 80
Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys
85 90 95
Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys
100 105 110
Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Ala Glu Ala Ala Ala
115 120 125
Lys Glu Ala Ala Ala Lys Ala Thr Ser Leu Ile His Ser Leu Ile Glu
130 135 140
Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu
145 150 155 160
Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu
165 170 175
Trp Tyr Ile Lys Leu Phe Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala
180 185 190
Ala Lys Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu
195 200 205
Gly Gly Glu Arg Asp Arg Asp Arg Ser Ile Ala Glu Ala Ala Ala Lys
210 215 220
Glu Ala Ala Ala Lys Ala Tyr His Arg Leu Arg Asp Leu Leu Leu Ile
225 230 235 240
Val Thr Arg Ile Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Glu
245 250 255
Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Gly Thr Asp Arg Val Ile
260 265 270
Glu Val Val Gln Gly Ala Cys Arg Ala Ile Arg His Ile Pro Arg Arg
275 280 285
Ile Arg Gln Gly Leu Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys
290 295 300
Ala Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
305 310 315 320
Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys
325 330 335
Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp
340 345 350
Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg
355 360 365
Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln
370 375 380
His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn
385 390 395 400
Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly
405 410 415
Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu
420 425 430
Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met
435 440 445
Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu
450 455 460
Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe
465 470 475 480
Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn
485 490 495
Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr
500 505 510
Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys
515 520
<210> 21
<211> 835
<212> PRT
<213> 合成的
<400> 21
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Val Gly Ile Gly Ala Leu Phe Leu Gly Phe Leu
20 25 30
Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val
35 40 45
Gln Ala Arg Gln Leu Leu Ser Ala Glu Ala Ala Ala Lys Glu Ala Ala
50 55 60
Ala Lys Ala Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly
65 70 75 80
Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys
85 90 95
Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys
100 105 110
Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Ala Glu Ala Ala Ala
115 120 125
Lys Glu Ala Ala Ala Lys Ala Thr Ser Leu Ile His Ser Leu Ile Glu
130 135 140
Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu
145 150 155 160
Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu
165 170 175
Trp Tyr Ile Lys Leu Phe Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala
180 185 190
Ala Lys Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu
195 200 205
Gly Gly Glu Arg Asp Arg Asp Arg Ser Ile Ala Glu Ala Ala Ala Lys
210 215 220
Glu Ala Ala Ala Lys Ala Tyr His Arg Leu Arg Asp Leu Leu Leu Ile
225 230 235 240
Val Thr Arg Ile Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Glu
245 250 255
Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Gly Thr Asp Arg Val Ile
260 265 270
Glu Val Val Gln Gly Ala Cys Arg Ala Ile Arg His Ile Pro Arg Arg
275 280 285
Ile Arg Gln Gly Leu Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys
290 295 300
Ala Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
305 310 315 320
Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys
325 330 335
Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp
340 345 350
Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg
355 360 365
Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln
370 375 380
His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn
385 390 395 400
Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly
405 410 415
Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu
420 425 430
Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met
435 440 445
Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu
450 455 460
Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe
465 470 475 480
Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn
485 490 495
Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr
500 505 510
Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys Ala Glu Ala Ala Ala Lys
515 520 525
Glu Ala Ala Ala Lys Ala Asn Met Trp Lys Asn Asp Met Val Glu Gln
530 535 540
Met His Glu Asp Ile Ile Ser Leu Trp Cys Thr Asp Leu Lys Asn Asp
545 550 555 560
Thr Asn Thr Asn Ser Ser Ser Gly Arg Met Ile Met Glu Lys Ala Glu
565 570 575
Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Thr Ser Ile Arg Gly Lys
580 585 590
Val Gln Lys Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile Ile Pro Ile
595 600 605
Asp Asn Asp Thr Thr Ser Tyr Lys Leu Thr Ser Cys Ala Glu Ala Ala
610 615 620
Ala Lys Glu Ala Ala Ala Lys Ala Pro Ile Pro Ile His Tyr Cys Ala
625 630 635 640
Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly
645 650 655
Thr Gly Pro Cys Thr Asn Val Ser Thr Val Cys Thr Arg Pro Asn Asn
660 665 670
Asn Thr Arg Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe
675 680 685
Val Thr Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Phe
690 695 700
Gly Asn Asn Lys Thr Ile Ile Phe Lys Gln Ser Ser Gly Gly Asp Ala
705 710 715 720
Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Ala Glu Ala Ala Ala
725 730 735
Lys Glu Ala Ala Ala Lys Ala Pro Cys Arg Ile Lys Gln Ile Ile Asn
740 745 750
Met Trp Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly
755 760 765
Gln Ile Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Leu Thr
770 775 780
Arg Asp Gly Gly Asn Ser Asn Asn Glu Ser Glu Ile Phe Arg Pro Gly
785 790 795 800
Gly Gly Asp Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Ile
805 810 815
Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln
820 825 830
Arg Glu Lys
835
<210> 22
<211> 714
<212> PRT
<213> 合成的
<400> 22
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
20 25 30
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
35 40 45
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
50 55 60
Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu
65 70 75 80
Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val
85 90 95
Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Glu Gln Ile Trp Asn
100 105 110
His Thr Thr Trp Met Glu Trp Asp Arg Glu Ile Asn Asn Tyr Thr Ser
115 120 125
Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
130 135 140
Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
145 150 155 160
Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys Leu Ala Glu Ala Ala
165 170 175
Ala Lys Glu Ala Ala Ala Lys Ala Ala Pro Asn Leu Leu Gly Gly Pro
180 185 190
Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser
195 200 205
Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp
210 215 220
Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr
225 230 235 240
Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val
245 250 255
Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu
260 265 270
Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg
275 280 285
Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val
290 295 300
Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr
305 310 315 320
Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr
325 330 335
Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu
340 345 350
Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys
355 360 365
Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu
370 375 380
Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly
385 390 395 400
Lys Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Asn Met Trp
405 410 415
Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp
420 425 430
Cys Thr Asp Leu Lys Asn Asp Thr Asn Thr Asn Ser Ser Ser Gly Arg
435 440 445
Met Ile Met Glu Lys Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys
450 455 460
Ala Thr Ser Ile Arg Gly Lys Val Gln Lys Glu Tyr Ala Phe Phe Tyr
465 470 475 480
Lys Leu Asp Ile Ile Pro Ile Asp Asn Asp Thr Thr Ser Tyr Lys Leu
485 490 495
Thr Ser Cys Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Pro
500 505 510
Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys
515 520 525
Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr
530 535 540
Val Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Arg Ile Arg Ile Gln
545 550 555 560
Arg Gly Pro Gly Arg Ala Phe Val Thr Ile Ala Glu Ala Ala Ala Lys
565 570 575
Glu Ala Ala Ala Lys Ala Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys
580 585 590
Gln Ser Ser Gly Gly Asp Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala
595 600 605
Lys Ala Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Pro Cys
610 615 620
Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly Lys Ala Met
625 630 635 640
Tyr Ala Pro Pro Ile Ser Gly Gln Ile Ala Glu Ala Ala Ala Lys Glu
645 650 655
Ala Ala Ala Lys Ala Leu Thr Arg Asp Gly Gly Asn Ser Asn Asn Glu
660 665 670
Ser Glu Ile Phe Arg Pro Gly Gly Gly Asp Ala Glu Ala Ala Ala Lys
675 680 685
Glu Ala Ala Ala Lys Ala Ile Glu Pro Leu Gly Val Ala Pro Thr Lys
690 695 700
Ala Lys Arg Arg Val Val Gln Arg Glu Lys
705 710
<210> 23
<211> 416
<212> PRT
<213> 合成的
<400> 23
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn
20 25 30
Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro Leu
35 40 45
Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys
50 55 60
Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn
65 70 75 80
Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val
85 90 95
Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr
100 105 110
Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu
115 120 125
Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser
130 135 140
Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg Glu
145 150 155 160
Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser Gln
165 170 175
Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Gly Gly Gly Gly Ser
180 185 190
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser
195 200 205
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu
210 215 220
Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro
225 230 235 240
Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala
245 250 255
Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val
260 265 270
Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe
275 280 285
Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr
290 295 300
Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile
305 310 315 320
Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys
325 330 335
Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp
340 345 350
Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp
355 360 365
Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser
370 375 380
Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly
385 390 395 400
Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
405 410 415
<210> 24
<211> 416
<212> PRT
<213> 合成的
<400> 24
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
20 25 30
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
35 40 45
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
50 55 60
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
65 70 75 80
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
85 90 95
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
100 105 110
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
115 120 125
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
130 135 140
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
145 150 155 160
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
165 170 175
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
180 185 190
Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
195 200 205
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
210 215 220
Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Phe Arg Pro Gly Gly Gly
245 250 255
Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile
260 265 270
Lys Ile Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val
275 280 285
Val Gln Arg Glu Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val
290 295 300
Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu
305 310 315 320
Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu
325 330 335
Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly
340 345 350
Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser
355 360 365
Trp Ser Asn Lys Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met
370 375 380
Gln Trp Glu Arg Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu
385 390 395 400
Leu Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu
405 410 415
<210> 25
<211> 416
<212> PRT
<213> 合成的
<400> 25
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
20 25 30
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
35 40 45
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
50 55 60
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
65 70 75 80
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
85 90 95
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
100 105 110
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
115 120 125
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
130 135 140
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
145 150 155 160
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
165 170 175
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
180 185 190
Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
195 200 205
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
210 215 220
Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Phe Arg Pro Gly Gly Gly
245 250 255
Asn Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val
260 265 270
Lys Ile Glu Pro Leu Gly Val Ala Pro Ser Arg Ala Lys Arg Arg Val
275 280 285
Val Glu Arg Glu Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val
290 295 300
Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu
305 310 315 320
Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu
325 330 335
Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly
340 345 350
Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro Trp Asn Ser Ser
355 360 365
Trp Ser Asn Lys Ser Met Asn Glu Ile Trp Asp Asn Met Thr Trp Leu
370 375 380
Gln Trp Asp Lys Glu Ile Ser Asn Tyr Thr Gln Ile Ile Tyr Asn Leu
385 390 395 400
Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu
405 410 415
<210> 26
<211> 416
<212> PRT
<213> 合成的
<400> 26
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
20 25 30
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
35 40 45
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
50 55 60
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
65 70 75 80
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
85 90 95
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
100 105 110
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
115 120 125
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
130 135 140
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
145 150 155 160
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
165 170 175
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
180 185 190
Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
195 200 205
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
210 215 220
Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Phe Arg Pro Gly Gly Gly
245 250 255
Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val
260 265 270
Glu Ile Lys Pro Leu Gly Ile Ala Pro Thr Gly Ala Lys Arg Arg Val
275 280 285
Val Glu Arg Glu Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val
290 295 300
Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Met
305 310 315 320
Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Thr Arg Val Leu
325 330 335
Ala Ile Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Leu Trp Gly
340 345 350
Cys Ser Gly Arg Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ser Ser
355 360 365
Trp Ser Asn Lys Thr Ser Ala Asp Ile Trp Asp Asn Met Thr Trp Met
370 375 380
Gln Trp Asp Arg Glu Ile Ser Asn Tyr Thr Asp Thr Ile Tyr Arg Leu
385 390 395 400
Leu Glu Asp Ser Gln Asn Gln Gln Glu Lys Asn Glu Lys Asp Leu Leu
405 410 415
<210> 27
<211> 416
<212> PRT
<213> 合成的
<400> 27
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
20 25 30
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
35 40 45
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
50 55 60
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
65 70 75 80
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
85 90 95
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
100 105 110
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
115 120 125
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
130 135 140
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
145 150 155 160
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
165 170 175
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
180 185 190
Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
195 200 205
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
210 215 220
Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Phe Arg Pro Gly Gly Gly
245 250 255
Asn Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val
260 265 270
Lys Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val
275 280 285
Val Glu Arg Glu Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val
290 295 300
Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu
305 310 315 320
Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu
325 330 335
Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly
340 345 350
Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ser Ser
355 360 365
Trp Ser Asn Lys Ser Leu Asn Lys Ile Trp Asp Asn Met Thr Trp Met
370 375 380
Glu Trp Asp Arg Glu Ile Ser Asn Tyr Thr Ser Ile Ile Tyr Ser Leu
385 390 395 400
Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu
405 410 415
<210> 28
<211> 425
<212> PRT
<213> 合成的
<400> 28
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Thr Asn Ile Thr Phe Ser Ala Glu Val Ala Glu Leu
20 25 30
Tyr Arg Leu Glu Leu Gly Asp Tyr Lys Leu Val Glu Val Thr Pro Ile
35 40 45
Gly Phe Ala Pro Thr Ala Glu Lys Arg Tyr Ser Ser Ala Pro Gly Arg
50 55 60
His Lys Arg Gly Val Leu Val Leu Gln Ser Arg Thr Leu Leu Ala Gly
65 70 75 80
Ile Val Gln Gln Gln Gln Gln Leu Leu Asp Val Val Lys Arg Gln Gln
85 90 95
Glu Met Leu Arg Leu Thr Val Trp Gly Thr Lys Asn Leu Gln Ala Arg
100 105 110
Val Thr Ala Ile Glu Lys Tyr Leu Ala Asp Gln Ala Arg Leu Asn Ser
115 120 125
Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp Val
130 135 140
Asn Asp Thr Leu Thr Pro Glu Trp Asn Asn Met Thr Trp Gln Glu Trp
145 150 155 160
Glu His Lys Ile Arg Phe Leu Glu Ala Asn Ile Ser Glu Ser Leu Glu
165 170 175
Gln Ala Gln Ile Gln Gln Glu Lys Asn Met Tyr Glu Leu Gln Lys Leu
180 185 190
Asn Ser Trp Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
195 200 205
Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys
210 215 220
Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val
225 230 235 240
Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe
245 250 255
Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu
260 265 270
Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His
275 280 285
Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala
290 295 300
Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg
305 310 315 320
Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met
325 330 335
Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro
340 345 350
Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn
355 360 365
Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val
370 375 380
Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr
385 390 395 400
Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu
405 410 415
Lys Ser Leu Ser His Ser Pro Gly Lys
420 425
<210> 29
<211> 425
<212> PRT
<213> 合成的
<400> 29
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
20 25 30
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
35 40 45
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
50 55 60
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
65 70 75 80
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
85 90 95
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
100 105 110
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
115 120 125
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
130 135 140
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
145 150 155 160
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
165 170 175
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
180 185 190
Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
195 200 205
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
210 215 220
Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Asn Ile Thr Phe Ser Ala
245 250 255
Glu Val Ala Glu Leu Tyr Arg Leu Glu Leu Gly Asp Tyr Lys Leu Val
260 265 270
Glu Val Thr Pro Ile Gly Phe Ala Pro Thr Ala Glu Lys Arg Tyr Ser
275 280 285
Ser Ala Pro Gly Arg His Lys Arg Gly Val Leu Val Leu Gln Ser Arg
290 295 300
Thr Leu Leu Ala Gly Ile Val Gln Gln Gln Gln Gln Leu Leu Asp Val
305 310 315 320
Val Lys Arg Gln Gln Glu Met Leu Arg Leu Thr Val Trp Gly Thr Lys
325 330 335
Asn Leu Gln Ala Arg Val Thr Ala Ile Glu Lys Tyr Leu Ala Asp Gln
340 345 350
Ala Arg Leu Asn Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr
355 360 365
Thr Val Pro Trp Val Asn Asp Thr Leu Thr Pro Glu Trp Asn Asn Met
370 375 380
Thr Trp Gln Glu Trp Glu His Lys Ile Arg Phe Leu Glu Ala Asn Ile
385 390 395 400
Ser Glu Ser Leu Glu Gln Ala Gln Ile Gln Gln Glu Lys Asn Met Tyr
405 410 415
Glu Leu Gln Lys Leu Asn Ser Trp Asp
420 425
<210> 30
<211> 467
<212> PRT
<213> 合成的
<400> 30
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Thr His Thr Leu Leu Lys Gly Ile Val Gln Gln Gln
20 25 30
Asp Asn Leu Leu Arg Ala Ile Gln Ala Gln Gln Gln Leu Leu Arg Leu
35 40 45
Ser Val Trp Gly Ile Arg Gln Leu Arg Ala Arg Leu Leu Ala Leu Glu
50 55 60
Thr Leu Leu Gln Asn Gln Gln Leu Leu Ser Leu Trp Gly Cys Lys Gly
65 70 75 80
Lys Leu Val Cys Tyr Thr Ser Val Lys Trp Asn Arg Thr Trp Ile Gly
85 90 95
Asn Glu Ser Ile Trp Asp Thr Leu Thr Trp Gln Glu Trp Asp Arg Gln
100 105 110
Ile Ser Asn Ile Ser Ser Thr Ile Tyr Glu Glu Ile Gln Lys Ala Gln
115 120 125
Val Gln Gln Glu Gln Asn Glu Lys Lys Leu Leu Glu Leu Asp Glu Trp
130 135 140
Ala Ser Ile Trp Asn Trp Leu Asp Ile Thr Lys Trp Leu Trp Tyr Ile
145 150 155 160
Lys Ile Ala Ile Ile Ile Val Gly Ala Leu Val Gly Val Arg Val Ile
165 170 175
Met Ile Val Leu Asn Ile Val Lys Asn Ile Arg Gln Gly Tyr Gln Pro
180 185 190
Leu Ser Leu Gln Ile Pro Asn His His Gln Glu Glu Ala Gly Thr Pro
195 200 205
Gly Arg Thr Gly Gly Gly Gly Gly Glu Glu Gly Arg Pro Arg Trp Ile
210 215 220
Pro Ser Pro Gln Gly Phe Leu Pro Leu Leu Tyr Thr Asp Leu Gly Gly
225 230 235 240
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Pro Glu
245 250 255
Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr
260 265 270
Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys
275 280 285
Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val
290 295 300
His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe
305 310 315 320
Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile
340 345 350
Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val
355 360 365
Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser
370 375 380
Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu
385 390 395 400
Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro
405 410 415
Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val
420 425 430
Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu
435 440 445
His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser
450 455 460
Pro Gly Lys
465
<210> 31
<211> 467
<212> PRT
<213> 合成的
<400> 31
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
20 25 30
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
35 40 45
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
50 55 60
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
65 70 75 80
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
85 90 95
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
100 105 110
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
115 120 125
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
130 135 140
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
145 150 155 160
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
165 170 175
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
180 185 190
Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
195 200 205
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
210 215 220
Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr His Thr Leu Leu Lys Gly
245 250 255
Ile Val Gln Gln Gln Asp Asn Leu Leu Arg Ala Ile Gln Ala Gln Gln
260 265 270
Gln Leu Leu Arg Leu Ser Val Trp Gly Ile Arg Gln Leu Arg Ala Arg
275 280 285
Leu Leu Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Ser Leu
290 295 300
Trp Gly Cys Lys Gly Lys Leu Val Cys Tyr Thr Ser Val Lys Trp Asn
305 310 315 320
Arg Thr Trp Ile Gly Asn Glu Ser Ile Trp Asp Thr Leu Thr Trp Gln
325 330 335
Glu Trp Asp Arg Gln Ile Ser Asn Ile Ser Ser Thr Ile Tyr Glu Glu
340 345 350
Ile Gln Lys Ala Gln Val Gln Gln Glu Gln Asn Glu Lys Lys Leu Leu
355 360 365
Glu Leu Asp Glu Trp Ala Ser Ile Trp Asn Trp Leu Asp Ile Thr Lys
370 375 380
Trp Leu Trp Tyr Ile Lys Ile Ala Ile Ile Ile Val Gly Ala Leu Val
385 390 395 400
Gly Val Arg Val Ile Met Ile Val Leu Asn Ile Val Lys Asn Ile Arg
405 410 415
Gln Gly Tyr Gln Pro Leu Ser Leu Gln Ile Pro Asn His His Gln Glu
420 425 430
Glu Ala Gly Thr Pro Gly Arg Thr Gly Gly Gly Gly Gly Glu Glu Gly
435 440 445
Arg Pro Arg Trp Ile Pro Ser Pro Gln Gly Phe Leu Pro Leu Leu Tyr
450 455 460
Thr Asp Leu
465
<210> 32
<211> 401
<212> PRT
<213> 合成的
<400> 32
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
20 25 30
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
35 40 45
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
50 55 60
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
65 70 75 80
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
85 90 95
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
100 105 110
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
115 120 125
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
130 135 140
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
145 150 155 160
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
165 170 175
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
180 185 190
Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
195 200 205
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
210 215 220
Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ser Met Thr Leu Thr Val
245 250 255
Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu
260 265 270
Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp
275 280 285
Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu
290 295 300
Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile
305 310 315 320
Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu
325 330 335
Glu Gln Ile Trp Asn His Thr Thr Trp Met Glu Trp Asp Arg Glu Ile
340 345 350
Asn Asn Tyr Thr Ser Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn
355 360 365
Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala
370 375 380
Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys
385 390 395 400
Leu
<210> 33
<211> 401
<212> PRT
<213> 合成的
<400> 33
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
20 25 30
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
35 40 45
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
50 55 60
Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu
65 70 75 80
Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val
85 90 95
Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Glu Gln Ile Trp Asn
100 105 110
His Thr Thr Trp Met Glu Trp Asp Arg Glu Ile Asn Asn Tyr Thr Ser
115 120 125
Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
130 135 140
Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
145 150 155 160
Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys Leu Gly Gly Gly Gly
165 170 175
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Pro Glu Val Ser
180 185 190
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
195 200 205
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
210 215 220
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
225 230 235 240
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
245 250 255
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
260 265 270
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
275 280 285
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
290 295 300
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
305 310 315 320
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
325 330 335
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
340 345 350
Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys
355 360 365
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
370 375 380
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
385 390 395 400
Lys
<210> 34
<211> 865
<212> PRT
<213> 合成的
<400> 34
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Arg
20 25 30
Trp Gly Trp Lys Trp Gly Thr Met Leu Leu Gly Ile Leu Met Ile Cys
35 40 45
Ser Ala Thr Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val
50 55 60
Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala
65 70 75 80
Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro
85 90 95
Thr Asp Pro Asn Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn
100 105 110
Phe Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile
115 120 125
Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro
130 135 140
Leu Cys Val Ser Leu Lys Cys Thr Asp Leu Gly Asn Ala Thr Asn Thr
145 150 155 160
Asn Ser Ser Asn Thr Asn Ser Ser Ser Gly Glu Met Met Met Glu Lys
165 170 175
Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Ser Thr Ser Ile Arg Gly
180 185 190
Lys Val Gln Lys Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile Ile Pro
195 200 205
Ile Asp Asn Asp Thr Thr Ser Tyr Thr Leu Thr Ser Cys Asn Thr Ser
210 215 220
Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile
225 230 235 240
His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys
245 250 255
Thr Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys
260 265 270
Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly
275 280 285
Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Ala Asn Phe Thr Asp
290 295 300
Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Gln Ser Val Glu Ile Asn
305 310 315 320
Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gln Arg
325 330 335
Gly Pro Gly Arg Ala Phe Val Thr Ile Gly Lys Ile Gly Asn Met Arg
340 345 350
Gln Ala His Cys Asn Ile Ser Arg Ala Lys Trp Asn Ala Thr Leu Lys
355 360 365
Gln Ile Ala Ser Lys Leu Arg Glu Gln Phe Gly Asn Asn Lys Thr Ile
370 375 380
Ile Phe Lys Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser
385 390 395 400
Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe
405 410 415
Asn Ser Thr Trp Phe Asn Ser Thr Trp Ser Thr Glu Gly Ser Asn Asn
420 425 430
Thr Glu Gly Ser Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Phe
435 440 445
Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile
450 455 460
Ser Gly Gln Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr
465 470 475 480
Arg Asp Gly Gly Asn Asn Asn Asn Gly Ser Glu Ile Phe Arg Pro Gly
485 490 495
Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys
500 505 510
Val Val Lys Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Gln Asn
515 520 525
His Val Val Gln Asn Glu His Gln Ala Val Gly Ile Gly Ala Leu Phe
530 535 540
Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Arg Ser Met
545 550 555 560
Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln
565 570 575
Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln
580 585 590
Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val
595 600 605
Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser
610 615 620
Gly Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser
625 630 635 640
Asn Lys Ser Leu Glu Gln Ile Trp Asn Asn Met Thr Trp Met Glu Trp
645 650 655
Asp Arg Glu Ile Asn Asn Tyr Thr Ser Leu Ile His Ser Leu Ile Glu
660 665 670
Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu
675 680 685
Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu
690 695 700
Trp Tyr Ile Lys Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe
705 710 715 720
Gln Thr His Leu Pro Thr Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile
725 730 735
Glu Glu Glu Gly Gly Glu Arg Asp Arg Asp Arg Ser Ile Arg Leu Val
740 745 750
Asn Gly Ser Leu Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu Cys Leu
755 760 765
Phe Ser Tyr His Arg Leu Arg Asp Leu Leu Leu Ile Val Thr Arg Ile
770 775 780
Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr Trp Trp
785 790 795 800
Asn Leu Leu Gln Tyr Trp Ser Gln Glu Leu Lys Asn Ser Ala Val Ser
805 810 815
Leu Leu Asn Ala Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val
820 825 830
Ile Glu Val Val Gln Gly Ala Cys Arg Ala Ile Arg His Ile Pro Arg
835 840 845
Arg Ile Arg Gln Gly Leu Glu Arg Ile Leu Leu His His His His His
850 855 860
His
865
<210> 35
<211> 849
<212> PRT
<213> 合成的
<400> 35
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Arg Val Arg Gly Ile Gln Arg Asn Trp Pro Gln
20 25 30
Trp Trp Ile Trp Gly Ile Leu Gly Phe Trp Met Val Met Ile Cys Arg
35 40 45
Val Val Val Gly Asn Met Trp Val Thr Val Tyr Tyr Gly Val Pro Val
50 55 60
Trp Lys Glu Ala Lys Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala
65 70 75 80
Tyr Glu Lys Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro
85 90 95
Thr Asp Pro Asn Pro Gln Glu Ile Val Leu Glu Asn Val Thr Glu Asn
100 105 110
Phe Asn Met Trp Lys Asn Asp Met Val Asp Gln Met His Glu Asp Ile
115 120 125
Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Ala Pro
130 135 140
Leu Cys Val Thr Leu Asn Cys Thr Asn Ser Asn Ala Thr Tyr Asn Asn
145 150 155 160
Ser Met His Gly Glu Ile Lys Asn Cys Ser Phe Asn Thr Thr Thr Glu
165 170 175
Ile Arg Asp Lys Lys Gln Asn Val Tyr Ala Leu Phe Tyr Lys Ser Asp
180 185 190
Val Val Pro Leu Lys Glu Asp Asn Asp Asn Ser Ser Tyr Ser Ser Tyr
195 200 205
Ile Leu Ile Asn Cys Asn Thr Ser Thr Ile Thr Gln Ala Cys Pro Lys
210 215 220
Val Thr Phe Asp Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Tyr
225 230 235 240
Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys
245 250 255
Ser Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val
260 265 270
Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Gly Glu Ile Ile
275 280 285
Ile Arg Ser Glu Asn Leu Thr Asn Asn Ile Lys Thr Ile Ile Val Gln
290 295 300
Leu Asn Thr Ser Arg Glu Ile Val Cys Thr Arg Pro Asn Asn Asn Thr
305 310 315 320
Arg Lys Ser Ile Arg Ile Gly Pro Gly Gln Ala Phe Tyr Ala Thr Asn
325 330 335
Glu Ile Ile Gly Asp Ile Arg Gln Ala Tyr Cys Asn Ile Ser Lys Thr
340 345 350
Glu Trp Ser Thr Thr Leu Asp Glu Val Lys Lys Lys Leu Ala Glu His
355 360 365
Phe Pro Asn Lys Thr Ile Arg Phe Ala Pro Pro Ile Gly Gly Asp Leu
370 375 380
Glu Ile Thr Thr His Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys
385 390 395 400
Asn Thr Thr Glu Leu Phe Asn Asp Asn Asn Ser Asp Asp Asn Ala Thr
405 410 415
Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Gly
420 425 430
Val Gly Arg Ala Met Tyr Ala Pro Pro Ile Glu Gly Ser Ile Thr Cys
435 440 445
Asn Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Thr Asn
450 455 460
Asn Thr Asp Glu Thr Phe Arg Pro Gly Gly Gly Asn Met Lys Asp Asn
465 470 475 480
Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile Lys Pro Leu
485 490 495
Gly Ile Ala Pro Thr Lys Ala Gln Asn His Val Val Gln Asn Glu His
500 505 510
Gln Ala Val Gly Leu Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala
515 520 525
Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg
530 535 540
Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala
545 550 555 560
Ile Glu Ala Gln Gln His Met Leu Gln Leu Thr Val Trp Gly Ile Lys
565 570 575
Gln Leu Gln Thr Arg Val Leu Ala Ile Glu Arg Tyr Leu Lys Asp Gln
580 585 590
Gln Leu Leu Gly Leu Trp Gly Cys Ser Gly Arg Leu Ile Cys Thr Thr
595 600 605
Ala Val Pro Trp Asn Ser Ser Trp Ser Asn Lys Thr Ser Ala Asp Ile
610 615 620
Trp Asp Asn Met Thr Trp Met Gln Trp Asp Arg Glu Ile Ser Asn Tyr
625 630 635 640
Thr Asp Thr Ile Tyr Arg Leu Leu Glu Asp Ser Gln Asn Gln Gln Glu
645 650 655
Lys Asn Glu Lys Asp Leu Leu Ala Leu Asp Ser Trp Lys Asn Leu Trp
660 665 670
Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys Lys Arg Val
675 680 685
Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu Thr Pro Asn Pro
690 695 700
Arg Glu Leu Asp Arg Leu Gly Arg Ile Glu Glu Glu Gly Gly Glu Gln
705 710 715 720
Asp Lys Asp Arg Ser Ile Arg Leu Val Asn Gly Phe Leu Ser Leu Ala
725 730 735
Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Gln Leu Arg
740 745 750
Asp Phe Ile Leu Ile Val Ala Arg Val Val Glu Leu Leu Gly Arg Ser
755 760 765
Ser Leu Arg Gly Leu Gln Arg Gly Trp Glu Ala Leu Lys Tyr Leu Gly
770 775 780
Asn Leu Val Gln Tyr Trp Gly Leu Glu Leu Lys Lys Ser Ala Ile Ser
785 790 795 800
Leu Phe Asp Asn Ile Ala Ile Thr Val Ala Glu Arg Thr Asp Arg Ile
805 810 815
Leu Glu Leu Ile Tyr Arg Ile Tyr Arg Ala Ile Arg Asn Ile Pro Arg
820 825 830
Arg Ile Arg Gln Gly Phe Glu Val Ala Leu Leu His His His His His
835 840 845
His
<210> 36
<211> 850
<212> PRT
<213> 合成的
<400> 36
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Arg Val Arg Gly Ile Gln Thr Ser Trp Gln Asn
20 25 30
Leu Trp Arg Trp Gly Thr Met Ile Leu Gly Met Leu Met Ile Tyr Ser
35 40 45
Ala Ala Glu Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp
50 55 60
Lys Asp Ala Glu Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr
65 70 75 80
Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr
85 90 95
Asp Pro Asn Pro Gln Glu Ile His Leu Glu Asn Val Thr Glu Asp Phe
100 105 110
Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Thr Asp Ile Ile
115 120 125
Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu
130 135 140
Cys Val Thr Leu Asp Cys Asn Ala Thr Ala Ser Asn Val Thr Asn Glu
145 150 155 160
Met Arg Asn Cys Ser Phe Asn Ile Thr Thr Glu Leu Lys Asp Lys Lys
165 170 175
Gln Gln Val Tyr Ser Leu Phe Tyr Lys Leu Asp Val Val Gln Ile Asn
180 185 190
Glu Lys Asn Glu Thr Asp Lys Tyr Arg Leu Ile Asn Cys Asn Thr Ser
195 200 205
Ala Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile
210 215 220
His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys Asp Thr
225 230 235 240
Glu Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys
245 250 255
Thr His Gly Ile Arg Pro Val Ile Ser Thr Gln Leu Leu Leu Asn Gly
260 265 270
Ser Leu Ala Glu Glu Gly Ile Gln Ile Arg Ser Glu Asn Ile Thr Asn
275 280 285
Asn Ala Lys Thr Ile Ile Val Gln Leu Asp Lys Ala Val Lys Ile Asn
290 295 300
Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Gly Val Arg Ile Gly Pro
305 310 315 320
Gly Gln Ala Phe Tyr Ala Thr Gly Gly Ile Ile Gly Asp Ile Arg Gln
325 330 335
Ala His Cys Asn Val Ser Arg Ala Lys Trp Asn Asp Thr Leu Arg Gly
340 345 350
Val Ala Lys Lys Leu Arg Glu His Phe Lys Asn Lys Thr Ile Ile Phe
355 360 365
Glu Lys Ser Ser Gly Gly Asp Ile Glu Ile Thr Thr His Ser Phe Asn
370 375 380
Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn Ser
385 390 395 400
Thr Trp Glu Ser Asn Ser Thr Glu Ser Asn Asn Thr Thr Ser Asn Asp
405 410 415
Thr Ile Thr Leu Thr Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln
420 425 430
Lys Val Gly Gln Ala Met Tyr Ala Pro Pro Ile Gln Gly Val Ile Arg
435 440 445
Cys Glu Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn
450 455 460
Asn Ser Thr Asn Glu Ile Phe Arg Pro Gly Gly Gly Asn Met Arg Asp
465 470 475 480
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro
485 490 495
Leu Gly Val Ala Pro Ser Lys Ala Gln Asn His Val Val Gln Asn Glu
500 505 510
His Gln Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu Gly Ala
515 520 525
Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Ala Gln Ala
530 535 540
Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg
545 550 555 560
Ala Ile Glu Ala Gln Gln His Met Leu Lys Leu Thr Val Trp Gly Ile
565 570 575
Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp
580 585 590
Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr
595 600 605
Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Lys Ser Met Asn Glu
610 615 620
Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys Glu Ile Ser Asn
625 630 635 640
Tyr Thr Gln Ile Ile Tyr Asn Leu Ile Glu Glu Ser Gln Asn Gln Gln
645 650 655
Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys Trp Ala Ser Leu
660 665 670
Trp Asn Trp Phe Asp Ile Ser Arg Trp Leu Trp Tyr Ile Lys Asn Arg
675 680 685
Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Ile Arg Thr Pro Asn
690 695 700
Pro Lys Glu Pro Asp Arg Leu Gly Arg Ile Asp Gly Glu Gly Gly Glu
705 710 715 720
Gln Asp Arg Asp Arg Ser Ile Arg Leu Val Ser Gly Phe Leu Ala Leu
725 730 735
Ala Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg Leu
740 745 750
Arg Asp Phe Ile Ser Ile Ala Ala Arg Thr Val Glu Leu Leu Gly His
755 760 765
Ser Ser Leu Lys Gly Leu Arg Leu Gly Trp Glu Gly Leu Lys Tyr Leu
770 775 780
Trp Asn Leu Leu Leu Tyr Trp Gly Arg Glu Leu Lys Thr Ser Ala Val
785 790 795 800
Asn Leu Val Asp Thr Ile Ala Ile Ala Val Ala Gly Trp Thr Asp Arg
805 810 815
Val Ile Glu Val Gly Gln Arg Ile Phe Arg Ala Ile Leu Asn Ile Pro
820 825 830
Arg Arg Ile Arg Gln Gly Leu Glu Arg Gly Leu Leu His His His His
835 840 845
His His
850
<210> 37
<211> 868
<212> PRT
<213> 合成的
<400> 37
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Val Lys Glu Thr Gln Met Asn Trp Pro Asn Leu Trp
20 25 30
Lys Trp Gly Thr Leu Ile Leu Gly Leu Val Ile Ile Cys Ser Ala Ala
35 40 45
Asp Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Arg Asp
50 55 60
Ala Asp Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala His Glu Thr
65 70 75 80
Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro
85 90 95
Asn Pro Gln Glu Ile His Leu Glu Asn Val Thr Glu Asn Phe Asn Met
100 105 110
Trp Lys Asn Asn Met Val Glu Gln Met Gln Glu Asp Val Ile Ser Leu
115 120 125
Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Phe Cys Val
130 135 140
Thr Leu Asn Cys Thr Asn Ala Thr Leu Thr Asn Val Thr Asn Ile Ala
145 150 155 160
Asn Ala Ser Asn Met Ile Gly Asn Ile Thr Asp Glu Ile Arg Asn Cys
165 170 175
Ser Phe Asn Met Thr Thr Glu Leu Arg Asp Lys Lys Gln Gln Val His
180 185 190
Ala Leu Phe Tyr Lys Leu Asp Ile Val Gln Ile Glu Asp Asn Lys Asn
195 200 205
Ser Ser Asn Asn Ser Ser Asn Ser Ser Lys Tyr Ser Glu Tyr Arg Leu
210 215 220
Ile Asn Cys Asn Thr Ser Val Ile Lys Gln Ala Cys Pro Lys Ile Ser
225 230 235 240
Phe Asp Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Tyr Ala Ile
245 250 255
Leu Lys Cys Asn Asp Lys Asn Phe Asn Gly Thr Gly Pro Cys Lys Asn
260 265 270
Val Ser Ser Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr
275 280 285
Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Ile Ile Arg
290 295 300
Ser Glu Asn Leu Thr Asn Asn Ala Lys Thr Ile Ile Val His Leu Asn
305 310 315 320
Lys Ser Val Glu Ile Asn Cys Thr Arg Pro Phe Tyr Thr Arg Ile Ser
325 330 335
Met Thr Arg Gly Pro Gly His Val Phe Tyr Arg Thr Gly Lys Ile Val
340 345 350
Gly Asp Pro Arg Lys Ala Tyr Cys Glu Ile Asn Gly Thr Lys Trp Asn
355 360 365
Glu Ala Leu Lys Gln Val Thr Glu Lys Leu Lys Glu His Phe Asn Lys
370 375 380
Thr Ile Ile Phe Gln Pro Pro Ser Gly Gly Asp Leu Glu Ile Thr Met
385 390 395 400
His His Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Thr Lys
405 410 415
Leu Phe Asn Ser Thr Gly Ile Gly Asn Glu Thr Met Lys Gly Tyr Asn
420 425 430
Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp
435 440 445
Gln Gly Ala Gly Gln Ala Met Tyr Ala Pro Pro Ile Lys Glu Arg Ile
450 455 460
Asn Cys Val Ser Asn Ile Thr Gly Ile Leu Leu Thr Arg Asp Gly Gly
465 470 475 480
Ile Asn Ser Thr Thr Asn Glu Thr Phe Arg Pro Gly Gly Gly Asn Ile
485 490 495
Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Gln Ile
500 505 510
Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Gln Asn His Val Val Gln
515 520 525
Asn Glu His Gln Ala Val Gly Ile Gly Ala Val Ile Phe Gly Phe Leu
530 535 540
Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Val
545 550 555 560
Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu
565 570 575
Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp
580 585 590
Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu
595 600 605
Lys Asp Gln Gln Phe Leu Gly Leu Trp Gly Cys Ser Gly Lys Ile Ile
610 615 620
Cys Thr Thr Ala Val Pro Trp Asn Ser Thr Trp Ser Asn Arg Ser Tyr
625 630 635 640
Glu Glu Ile Trp Asn Asn Met Thr Trp Ile Glu Trp Glu Arg Glu Ile
645 650 655
Ser Asn Tyr Thr Asn Gln Ile Tyr Glu Ile Leu Thr Glu Ser Gln Asp
660 665 670
Gln Gln Asp Arg Asn Glu Lys Asp Leu Leu Glu Leu Asp Lys Trp Ala
675 680 685
Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys
690 695 700
Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Ile Pro Ser
705 710 715 720
His His Gln Arg Glu Pro Asp Arg Pro Glu Gly Ile Glu Glu Gly Gly
725 730 735
Gly Glu Glu Gly Arg Asp Arg Ser Val Arg Leu Val Ser Gly Phe Leu
740 745 750
Ala Leu Ala Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His
755 760 765
Arg Leu Arg Asp Leu Leu Ser Ile Ala Thr Arg Thr Val Glu Leu Leu
770 775 780
Gly His Ser Ser Leu Lys Gly Leu Arg Arg Gly Trp Glu Gly Leu Lys
785 790 795 800
Tyr Leu Gly Asn Leu Leu Leu Tyr Trp Gly Gln Glu Leu Lys Ile Ser
805 810 815
Ala Ile Ser Leu Leu Asp Thr Thr Ala Ile Ala Val Ala Gly Trp Thr
820 825 830
Asp Arg Val Ile Glu Val Ala Gln Arg Ala Trp Arg Ala Ile Leu His
835 840 845
Ile Pro Arg Arg Ile Arg Gln Gly Leu Glu Arg Ser Leu Leu His His
850 855 860
His His His His
865
<210> 38
<211> 879
<212> PRT
<213> 合成的
<400> 38
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Lys
20 25 30
Trp Gly Trp Arg Trp Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys
35 40 45
Asn Val Ala Glu Glu Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro
50 55 60
Val Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys
65 70 75 80
Ala Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val
85 90 95
Pro Thr Asp Pro Asn Pro Gln Glu Ile Glu Leu Glu Asn Val Thr Glu
100 105 110
Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp
115 120 125
Ile Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr
130 135 140
Pro Leu Cys Val Thr Leu Asn Cys Thr Asp Leu Arg Asn Ala Thr Asn
145 150 155 160
Gly Asn Asp Thr Asn Thr Thr Ser Ser Ser Arg Glu Met Met Gly Gly
165 170 175
Gly Glu Met Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Arg Asp
180 185 190
Lys Lys Gln Lys Val Tyr Ala Leu Phe Tyr Lys Leu Asp Ile Val Pro
195 200 205
Ile Asp Asn Asn Lys Asn Ser Ser Asn Asn Ser Ser Asn Ser Ser Ser
210 215 220
Asn Asn Arg Tyr Arg Leu Ile Asn Cys Asn Thr Ser Val Ile Thr Gln
225 230 235 240
Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala
245 250 255
Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys Asp Lys Lys Phe Asn Gly
260 265 270
Thr Gly Pro Cys Ser Asn Val Ser Thr Val Gln Cys Thr His Gly Ile
275 280 285
Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu
290 295 300
Glu Glu Ile Val Ile Arg Ser Glu Asn Phe Thr Asn Asn Ala Lys Thr
305 310 315 320
Ile Ile Val Gln Leu Asn Glu Ser Val Glu Ile Asn Cys Thr Arg Pro
325 330 335
Asn Asn Asn Thr Arg Lys Ser Ile His Ile Gly Pro Gly Arg Ala Phe
340 345 350
Tyr Thr Thr Gly Glu Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn
355 360 365
Leu Ser Arg Ala Lys Trp Asn Asp Thr Leu Asn Lys Val Val Ile Lys
370 375 380
Leu Arg Glu His Phe Gly Asn Lys Thr Ile Val Phe Lys His Ser Ser
385 390 395 400
Gly Gly Asp Pro Glu Ile Thr Thr His Ser Phe Asn Cys Gly Gly Glu
405 410 415
Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Ser Thr Trp Glu Ser
420 425 430
Asn Ser Thr Glu Ser Asn Asn Thr Val Glu Asn Asn Thr Ile Thr Leu
435 440 445
Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly Arg
450 455 460
Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln Ile Arg Cys Ser Ser Asn
465 470 475 480
Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Pro Asn Ala Asn Thr
485 490 495
Thr Glu Val Phe Arg Pro Gly Gly Gly Asn Met Arg Asp Asn Trp Arg
500 505 510
Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val
515 520 525
Ala Pro Thr Lys Ala Gln Asn His Val Val Gln Asn Glu His Gln Ala
530 535 540
Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser
545 550 555 560
Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu
565 570 575
Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu
580 585 590
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
595 600 605
Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu
610 615 620
Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val
625 630 635 640
Pro Trp Asn Ser Ser Trp Ser Asn Lys Ser Leu Asn Lys Ile Trp Asp
645 650 655
Asn Met Thr Trp Met Glu Trp Asp Arg Glu Ile Ser Asn Tyr Thr Ser
660 665 670
Ile Ile Tyr Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
675 680 685
Glu Gln Asp Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
690 695 700
Phe Asp Ile Thr Glu Trp Leu Trp Tyr Ile Lys Asn Arg Val Arg Gln
705 710 715 720
Gly Tyr Ser Pro Leu Ser Phe Gln Thr His Leu Pro Ala Ser Arg Glu
725 730 735
Pro Asp Arg Pro Gly Gly Ile Glu Glu Glu Gly Gly Glu Arg Asp Arg
740 745 750
Asp Arg Ser Gly Arg Leu Val Asn Gly Phe Leu Ala Leu Ala Trp Asp
755 760 765
Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Leu
770 775 780
Leu Leu Ile Val Thr Arg Ile Val Glu Leu Leu Gly Arg Ser Ser Leu
785 790 795 800
Arg Gly Leu Gln Arg Gly Trp Glu Phe Leu Lys Tyr Leu Trp Asn Leu
805 810 815
Leu Gln Tyr Trp Gly Gln Glu Leu Lys Asn Ser Ala Val Ser Leu Leu
820 825 830
Asp Thr Ile Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile Glu
835 840 845
Val Leu Gln Arg Ala Val Arg Ala Ile Leu His Ile Pro Arg Arg Ile
850 855 860
Arg Gln Gly Leu Glu Arg Ala Leu Leu His His His His His His
865 870 875
<210> 39
<211> 829
<212> PRT
<213> 人类免疫缺陷病毒
<400> 39
Met Arg Val Met Gly Ile Gln Arg Asn Cys Gln His Leu Trp Arg Trp
1 5 10 15
Gly Ile Leu Ile Phe Gly Met Leu Ile Ile Cys Ser Ala Ala Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Asn
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Val Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Val Asn Ala Thr Asn Asn Thr Thr Asn Asn Glu Glu
130 135 140
Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Arg Asp Lys Lys
145 150 155 160
Lys Lys Val Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Pro Ile Asp
165 170 175
Asp Asn Asn Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr
180 185 190
Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys
195 200 205
Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe Asn
210 215 220
Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly
225 230 235 240
Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala
245 250 255
Glu Glu Glu Ile Ile Ile Arg Ser Glu Asn Ile Thr Asn Asn Ala Lys
260 265 270
Thr Ile Ile Val Gln Leu Asn Glu Ser Val Glu Ile Asn Cys Thr Arg
275 280 285
Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly Pro Gly Gln Ala
290 295 300
Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys
305 310 315 320
Asn Ile Ser Arg Thr Lys Trp Asn Lys Thr Leu Gln Gln Val Ala Lys
325 330 335
Lys Leu Arg Glu His Phe Asn Lys Thr Ile Ile Phe Asn Pro Ser Ser
340 345 350
Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Gly Gly Glu
355 360 365
Phe Phe Tyr Cys Asn Thr Ser Glu Leu Phe Asn Ser Thr Trp Asn Gly
370 375 380
Thr Asn Asn Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn
385 390 395 400
Met Trp Gln Gly Val Gly Gln Ala Met Tyr Ala Pro Pro Ile Glu Gly
405 410 415
Lys Ile Arg Cys Thr Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp
420 425 430
Gly Gly Asn Asn Asn Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp Met
435 440 445
Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile
450 455 460
Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Glu
465 470 475 480
Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu
485 490 495
Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Val
500 505 510
Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu
515 520 525
Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp
530 535 540
Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu
545 550 555 560
Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile
565 570 575
Cys Thr Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Lys Ser Gln
580 585 590
Asp Glu Ile Trp Asp Asn Met Thr Trp Met Glu Trp Asp Lys Glu Ile
595 600 605
Asn Asn Tyr Thr Asp Ile Ile Tyr Ser Leu Ile Glu Glu Ser Gln Asn
610 615 620
Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Ala Leu Asp Lys Trp Ala
625 630 635 640
Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile Lys
645 650 655
Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Val Phe
660 665 670
Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu
675 680 685
Ser Phe Gln Thr Leu Ile Pro Asn Pro Arg Gly Pro Asp Arg Pro Glu
690 695 700
Gly Ile Glu Glu Glu Gly Gly Glu Gln Asp Arg Asp Arg Ser Ile Arg
705 710 715 720
Leu Val Asn Gly Phe Leu Ala Leu Ala Trp Asp Asp Leu Arg Ser Leu
725 730 735
Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Leu Ile Leu Ile Ala Ala
740 745 750
Arg Thr Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr
755 760 765
Leu Trp Asn Leu Leu Gln Tyr Trp Gly Gln Glu Leu Lys Asn Ser Ala
770 775 780
Ile Ser Leu Leu Asp Thr Thr Ala Ile Ala Val Ala Glu Gly Thr Asp
785 790 795 800
Arg Val Ile Glu Val Val Gln Arg Val Cys Arg Ala Ile Leu Asn Ile
805 810 815
Pro Arg Arg Ile Arg Gln Gly Phe Glu Arg Ala Leu Leu
820 825
<210> 40
<211> 830
<212> PRT
<213> 人类免疫缺陷病毒
<400> 40
Met Arg Val Met Gly Ile Gln Arg Asn Cys Gln His Leu Trp Arg Trp
1 5 10 15
Gly Ile Leu Ile Phe Gly Met Leu Met Ile Cys Ser Ala Ala Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Asn
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Val Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Val Asn Ala Thr Asn Asn Ser Thr Asn Met Gly Glu
130 135 140
Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Arg Asp Lys Lys
145 150 155 160
Gln Lys Val Tyr Ala Leu Phe Tyr Arg Leu Asp Val Val Pro Ile Asn
165 170 175
Asp Asn Asn Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr
180 185 190
Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys
195 200 205
Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe Asn
210 215 220
Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly
225 230 235 240
Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala
245 250 255
Glu Glu Glu Ile Ile Ile Arg Ser Glu Asn Ile Thr Asp Asn Ala Lys
260 265 270
Thr Ile Ile Val Gln Leu Asn Glu Ser Val Glu Ile Asn Cys Thr Arg
275 280 285
Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly Pro Gly Gln Ala
290 295 300
Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys
305 310 315 320
Asn Ile Ser Gly Ala Glu Trp Asn Lys Thr Leu Gln Gln Val Ala Ala
325 330 335
Lys Leu Arg Glu His Phe Asn Asn Lys Thr Ile Ile Phe Lys Pro Ser
340 345 350
Ser Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Gly Gly
355 360 365
Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn Ser Thr Trp Asn
370 375 380
Gly Thr Asn Glu Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val
385 390 395 400
Asn Met Trp Gln Arg Val Gly Gln Ala Met Tyr Ala Pro Pro Ile Ala
405 410 415
Gly Asn Ile Thr Cys Lys Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg
420 425 430
Asp Gly Gly Thr Asn Asn Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp
435 440 445
Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys
450 455 460
Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val
465 470 475 480
Glu Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe
485 490 495
Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu Thr
500 505 510
Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn
515 520 525
Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val
530 535 540
Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr
545 550 555 560
Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu
565 570 575
Ile Cys Thr Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Lys Ser
580 585 590
Gln Asp Glu Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg Glu
595 600 605
Ile Ser Asn Tyr Thr Asp Ile Ile Tyr Ser Leu Ile Glu Glu Ser Gln
610 615 620
Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys Trp
625 630 635 640
Ala Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile
645 650 655
Lys Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Val
660 665 670
Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro
675 680 685
Leu Ser Phe Gln Thr Leu Ile Pro Asn Pro Arg Gly Pro Asp Arg Pro
690 695 700
Gly Gly Ile Glu Glu Glu Gly Gly Glu Gln Asp Arg Asp Arg Ser Ile
705 710 715 720
Arg Leu Val Ser Gly Phe Leu Ala Leu Ala Trp Asp Asp Leu Arg Ser
725 730 735
Leu Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Phe Ile Leu Ile Ala
740 745 750
Ala Arg Thr Val Glu Leu Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys
755 760 765
Tyr Leu Trp Asn Leu Leu Gln Tyr Trp Gly Gln Glu Leu Lys Asn Ser
770 775 780
Ala Ile Ser Leu Leu Asp Thr Thr Ala Ile Ala Val Ala Glu Gly Thr
785 790 795 800
Asp Arg Val Ile Glu Val Val Gln Arg Ala Cys Arg Ala Ile Leu His
805 810 815
Ile Pro Arg Arg Ile Arg Gln Gly Phe Glu Arg Ala Leu Leu
820 825 830
<210> 41
<211> 845
<212> PRT
<213> 人类免疫缺陷病毒
<400> 41
Met Arg Val Met Gly Ile Gln Arg Asn Cys Gln His Leu Leu Arg Trp
1 5 10 15
Gly Thr Met Ile Leu Gly Met Ile Ile Ile Cys Ser Ala Ala Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Asp Ala Glu
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Glu Thr Glu Met
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile His Leu Glu Asn Val Thr Glu Glu Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Thr Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Ser Asn Val Asn Val Thr Asn Asn Thr Thr Asn Thr His Glu
130 135 140
Glu Glu Ile Lys Asn Cys Ser Phe Asn Met Thr Thr Glu Leu Arg Asp
145 150 155 160
Lys Lys Gln Lys Val Tyr Ser Leu Phe Tyr Arg Leu Asp Val Val Gln
165 170 175
Ile Asn Glu Asn Asn Ser Asn Ser Ser Tyr Arg Leu Ile Asn Cys Asn
180 185 190
Thr Ser Ala Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile
195 200 205
Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys
210 215 220
Asp Lys Glu Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val
225 230 235 240
Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu
245 250 255
Asn Gly Ser Leu Ala Glu Glu Glu Val Ile Ile Arg Ser Glu Asn Ile
260 265 270
Thr Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Thr Lys Pro Val Lys
275 280 285
Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile
290 295 300
Gly Pro Gly Gln Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile
305 310 315 320
Arg Gln Ala His Cys Asn Val Ser Arg Ser Glu Trp Asn Lys Thr Leu
325 330 335
Gln Lys Val Ala Lys Gln Leu Arg Lys Tyr Phe Lys Asn Lys Thr Ile
340 345 350
Ile Phe Thr Asn Ser Ser Gly Gly Asp Leu Glu Ile Thr Thr His Ser
355 360 365
Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe
370 375 380
Asn Ser Thr Trp Asn Asn Gly Thr Met Lys Asn Thr Ile Thr Leu Pro
385 390 395 400
Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Arg Ala Gly Gln Ala
405 410 415
Met Tyr Ala Pro Pro Ile Gln Gly Val Ile Arg Cys Glu Ser Asn Ile
420 425 430
Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Asn Thr Asn Glu
435 440 445
Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu
450 455 460
Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala Pro
465 470 475 480
Thr Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val Gly
485 490 495
Ile Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met
500 505 510
Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser
515 520 525
Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln
530 535 540
Gln His Leu Leu Lys Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala
545 550 555 560
Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly
565 570 575
Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro Trp
580 585 590
Asn Ser Ser Trp Ser Asn Lys Ser Gln Asn Glu Ile Trp Asp Asn Met
595 600 605
Thr Trp Leu Gln Trp Asp Lys Glu Ile Ser Asn Tyr Thr His Ile Ile
610 615 620
Tyr Asn Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln
625 630 635 640
Asp Leu Leu Ala Leu Asp Lys Trp Ala Asn Leu Trp Asn Trp Phe Asp
645 650 655
Ile Ser Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val Gly
660 665 670
Gly Leu Ile Gly Leu Arg Ile Val Phe Ala Val Leu Ser Val Ile Asn
675 680 685
Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr His Thr Pro
690 695 700
Asn Pro Arg Gly Leu Asp Arg Pro Gly Arg Ile Glu Glu Glu Gly Gly
705 710 715 720
Glu Gln Gly Arg Asp Arg Ser Ile Arg Leu Val Ser Gly Phe Leu Ala
725 730 735
Leu Ala Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg
740 745 750
Leu Arg Asp Phe Ile Leu Ile Ala Ala Arg Thr Val Glu Leu Leu Gly
755 760 765
His Ser Ser Leu Lys Gly Leu Arg Leu Gly Trp Glu Gly Leu Lys Tyr
770 775 780
Leu Trp Asn Leu Leu Leu Tyr Trp Gly Arg Glu Leu Lys Ile Ser Ala
785 790 795 800
Ile Asn Leu Val Asp Thr Ile Ala Ile Ala Val Ala Gly Trp Thr Asp
805 810 815
Arg Val Ile Glu Ile Gly Gln Arg Ile Gly Arg Ala Ile Leu His Ile
820 825 830
Pro Arg Arg Ile Arg Gln Gly Leu Glu Arg Ala Leu Leu
835 840 845
<210> 42
<211> 845
<212> PRT
<213> 人类免疫缺陷病毒
<400> 42
Met Arg Val Met Gly Ile Gln Arg Asn Cys Gln His Leu Trp Arg Trp
1 5 10 15
Gly Thr Met Ile Phe Gly Met Ile Ile Ile Cys Ser Ala Ala Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Asp Ala Glu
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Asp Leu Glu Asn Val Thr Glu Glu Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Ala Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Ser Asn Val Asn Val Thr Asn Asn Thr Thr Asn Thr His Glu
130 135 140
Glu Glu Ile Lys Asn Cys Ser Phe Asn Met Thr Thr Glu Leu Arg Asp
145 150 155 160
Lys Lys Gln Lys Val Tyr Ser Leu Phe Tyr Arg Leu Asp Val Val Pro
165 170 175
Ile Asn Glu Asn Asn Ser Asn Ser Ser Tyr Arg Leu Ile Asn Cys Asn
180 185 190
Thr Ser Ala Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile
195 200 205
Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys
210 215 220
Asp Lys Glu Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val
225 230 235 240
Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu
245 250 255
Asn Gly Ser Leu Ala Glu Glu Glu Val Met Ile Arg Ser Glu Asn Ile
260 265 270
Thr Asp Asn Ala Lys Thr Ile Ile Val Gln Leu Thr Glu Pro Val Lys
275 280 285
Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile
290 295 300
Gly Pro Gly Gln Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile
305 310 315 320
Arg Gln Ala His Cys Asn Val Ser Arg Thr Glu Trp Asn Lys Thr Leu
325 330 335
Gln Lys Val Ala Ala Gln Leu Arg Lys His Phe Asn Asn Lys Thr Ile
340 345 350
Ile Phe Asn Ser Ser Ser Gly Gly Asp Leu Glu Ile Thr Thr His Ser
355 360 365
Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe
370 375 380
Asn Ser Thr Trp Asn Asn Gly Thr Met Lys Asp Thr Ile Thr Leu Pro
385 390 395 400
Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Arg Val Gly Gln Ala
405 410 415
Met Tyr Ala Pro Pro Ile Gln Gly Val Ile Arg Cys Glu Ser Asn Ile
420 425 430
Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Asn Thr Asn Glu
435 440 445
Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu
450 455 460
Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala Pro
465 470 475 480
Thr Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val Gly
485 490 495
Leu Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met
500 505 510
Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser
515 520 525
Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln
530 535 540
Gln His Leu Leu Lys Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala
545 550 555 560
Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly
565 570 575
Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro Trp
580 585 590
Asn Ser Ser Trp Ser Asn Lys Ser Gln Asp Glu Ile Trp Asp Asn Met
595 600 605
Thr Trp Leu Gln Trp Asp Lys Glu Ile Ser Asn Tyr Thr Asp Ile Ile
610 615 620
Tyr Asn Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln
625 630 635 640
Asp Leu Leu Ala Leu Asp Lys Trp Ala Asn Leu Trp Asn Trp Phe Asp
645 650 655
Ile Ser Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val Gly
660 665 670
Gly Leu Ile Gly Leu Arg Ile Val Phe Ala Val Leu Ser Val Ile Asn
675 680 685
Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu Thr Pro
690 695 700
Asn Pro Glu Gly Pro Asp Arg Pro Gly Arg Ile Glu Glu Glu Gly Gly
705 710 715 720
Glu Gln Gly Arg Asp Arg Ser Ile Arg Leu Val Ser Gly Phe Leu Ala
725 730 735
Leu Ala Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg
740 745 750
Leu Arg Asp Phe Ile Leu Ile Ala Ala Arg Thr Val Glu Leu Leu Gly
755 760 765
Arg Ser Ser Leu Lys Gly Leu Arg Leu Gly Trp Glu Gly Leu Lys Tyr
770 775 780
Leu Trp Asn Leu Leu Leu Tyr Trp Gly Arg Glu Leu Lys Ile Ser Ala
785 790 795 800
Ile Asn Leu Leu Asp Thr Ile Ala Ile Ala Val Ala Gly Trp Thr Asp
805 810 815
Arg Val Ile Glu Ile Gly Gln Arg Ile Cys Arg Ala Ile Leu Asn Ile
820 825 830
Pro Arg Arg Ile Arg Gln Gly Leu Glu Arg Ala Leu Leu
835 840 845
<210> 43
<211> 843
<212> PRT
<213> 人类免疫缺陷病毒
<400> 43
Met Arg Val Met Gly Thr Gln Arg Asn Tyr Gln His Leu Trp Arg Trp
1 5 10 15
Gly Ile Leu Ile Leu Gly Met Leu Ile Met Cys Lys Ala Thr Asp Leu
20 25 30
Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Asp Ala Asp Thr
35 40 45
Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val His
50 55 60
Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro Gln
65 70 75 80
Glu Val Asn Leu Glu Asn Val Thr Glu Asp Phe Asn Met Trp Lys Asn
85 90 95
Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp Gln
100 105 110
Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu Asn
115 120 125
Cys Ser Asn Ala Asn Thr Thr Asn Asn Ser Thr Met Glu Glu Ile Lys
130 135 140
Asn Cys Ser Tyr Asn Ile Thr Thr Glu Leu Arg Asp Lys Thr Gln Lys
145 150 155 160
Val Tyr Ser Leu Phe Tyr Lys Leu Asp Val Val Gln Leu Asp Glu Ser
165 170 175
Asn Lys Ser Glu Tyr Tyr Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala
180 185 190
Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His
195 200 205
Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys Asp Pro Arg
210 215 220
Phe Asn Gly Thr Gly Ser Cys Asn Asn Val Ser Ser Val Gln Cys Thr
225 230 235 240
His Gly Ile Lys Pro Val Ala Ser Thr Gln Leu Leu Leu Asn Gly Ser
245 250 255
Leu Ala Glu Gly Lys Val Met Ile Arg Ser Glu Asn Ile Thr Asn Asn
260 265 270
Ala Lys Asn Ile Ile Val Gln Phe Asn Lys Pro Val Pro Ile Thr Cys
275 280 285
Ile Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Phe Gly Pro Gly
290 295 300
Gln Ala Phe Tyr Thr Asn Asp Ile Ile Gly Asp Ile Arg Gln Ala His
305 310 315 320
Cys Asn Ile Asn Lys Thr Lys Trp Asn Ala Thr Leu Gln Lys Val Ala
325 330 335
Glu Gln Leu Arg Glu His Phe Pro Asn Lys Thr Ile Ile Phe Thr Asn
340 345 350
Ser Ser Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Gly
355 360 365
Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gly Leu Phe Asn Ser Thr Trp
370 375 380
Lys Asn Gly Thr Thr Asn Asn Thr Glu Gln Met Ile Thr Leu Pro Cys
385 390 395 400
Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Arg Val Gly Arg Ala Met
405 410 415
Tyr Ala Pro Pro Ile Ala Gly Val Ile Lys Cys Thr Ser Asn Ile Thr
420 425 430
Gly Ile Ile Leu Thr Arg Asp Gly Gly Asn Asn Glu Thr Glu Thr Phe
435 440 445
Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr
450 455 460
Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala Pro Thr Arg
465 470 475 480
Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val Gly Met Gly
485 490 495
Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala
500 505 510
Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile
515 520 525
Val Gln Gln Gln Ser Asn Leu Leu Lys Ala Ile Glu Ala Gln Gln His
530 535 540
Leu Leu Lys Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val
545 550 555 560
Leu Ala Leu Glu Arg Tyr Leu Gln Asp Gln Gln Leu Leu Gly Ile Trp
565 570 575
Gly Cys Ser Gly Lys Leu Ile Cys Ala Thr Thr Val Pro Trp Asn Ser
580 585 590
Ser Trp Ser Asn Lys Thr Gln Glu Glu Ile Trp Asn Asn Met Thr Trp
595 600 605
Leu Gln Trp Asp Lys Glu Ile Ser Asn Tyr Thr Asn Ile Ile Tyr Lys
610 615 620
Leu Leu Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu
625 630 635 640
Leu Ala Leu Asp Lys Trp Ala Asn Leu Trp Asn Trp Phe Asn Ile Thr
645 650 655
Asn Trp Leu Trp Tyr Ile Arg Ile Phe Ile Met Ile Val Gly Gly Leu
660 665 670
Ile Gly Leu Arg Ile Val Ile Ala Ile Ile Ser Val Val Asn Arg Val
675 680 685
Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Ile Pro Thr Pro Asn Pro
690 695 700
Glu Gly Leu Asp Arg Pro Gly Arg Ile Glu Glu Gly Gly Gly Glu Gln
705 710 715 720
Gly Arg Asp Arg Ser Ile Arg Leu Val Ser Gly Phe Leu Ala Leu Ala
725 730 735
Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg Leu Arg
740 745 750
Asp Cys Ile Leu Ile Ala Ala Arg Thr Val Glu Leu Leu Gly His Ser
755 760 765
Ser Leu Lys Gly Leu Arg Leu Gly Trp Glu Gly Leu Lys Tyr Leu Trp
770 775 780
Asn Leu Leu Leu Tyr Trp Gly Arg Glu Leu Lys Asn Ser Ala Ile Ser
785 790 795 800
Leu Leu Asp Thr Ile Ala Val Ala Val Ala Glu Trp Thr Asp Arg Val
805 810 815
Ile Glu Ile Gly Gln Arg Ala Cys Arg Ala Ile Leu Asn Ile Pro Arg
820 825 830
Arg Ile Arg Gln Gly Phe Glu Arg Ala Leu Leu
835 840
<210> 44
<211> 841
<212> PRT
<213> 人类免疫缺陷病毒
<400> 44
Met Arg Val Lys Gly Ile Arg Lys Asn Tyr Gln His Leu Trp Arg Trp
1 5 10 15
Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys Ser Ala Ala Glu Lys
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Leu Met Asn Ala Thr Asn Thr Asn Thr Thr Ile Ile
130 135 140
Tyr Arg Trp Arg Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr
145 150 155 160
Ser Ile Arg Asp Lys Val Gln Lys Glu Tyr Ala Leu Phe Tyr Lys Leu
165 170 175
Asp Val Val Pro Ile Asp Asn Asp Asn Thr Ser Tyr Arg Leu Ile Ser
180 185 190
Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu
195 200 205
Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys
210 215 220
Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser
225 230 235 240
Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu
245 250 255
Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu
260 265 270
Asn Phe Thr Asp Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Glu Ser
275 280 285
Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile
290 295 300
His Ile Gly Pro Gly Arg Ala Phe Tyr Thr Thr Gly Glu Ile Ile Gly
305 310 315 320
Asp Ile Arg Gln Ala His Cys Asn Ile Ser Arg Ala Lys Trp Asn Asn
325 330 335
Thr Leu Lys Gln Ile Val Lys Lys Leu Arg Glu Gln Phe Gly Asn Lys
340 345 350
Thr Ile Val Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met
355 360 365
His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln
370 375 380
Leu Phe Asn Ser Thr Trp Asn Gly Thr Trp Asn Asn Thr Glu Gly Asn
385 390 395 400
Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu
405 410 415
Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln Ile Arg Cys
420 425 430
Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn
435 440 445
Glu Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp
450 455 460
Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly
465 470 475 480
Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg
485 490 495
Ala Val Gly Ile Gly Ala Met Phe Leu Gly Phe Leu Gly Ala Ala Gly
500 505 510
Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln
515 520 525
Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile
530 535 540
Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln
545 550 555 560
Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln
565 570 575
Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala
580 585 590
Val Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Asp Glu Ile Trp
595 600 605
Asp Asn Met Thr Trp Met Glu Trp Glu Arg Glu Ile Asp Asn Tyr Thr
610 615 620
Ser Leu Ile Tyr Thr Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys
625 630 635 640
Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn
645 650 655
Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met
660 665 670
Ile Val Gly Gly Leu Val Gly Leu Arg Ile Val Phe Ala Val Leu Ser
675 680 685
Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr
690 695 700
Arg Leu Pro Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu
705 710 715 720
Glu Gly Gly Glu Arg Asp Arg Asp Arg Ser Gly Arg Leu Val Asp Gly
725 730 735
Phe Leu Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser
740 745 750
Tyr His Arg Leu Arg Asp Leu Leu Leu Ile Val Thr Arg Ile Val Glu
755 760 765
Leu Leu Gly Arg Arg Gly Trp Glu Val Leu Lys Tyr Trp Trp Asn Leu
770 775 780
Leu Gln Tyr Trp Ser Gln Glu Leu Lys Asn Ser Ala Val Ser Leu Leu
785 790 795 800
Asn Ala Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile Glu
805 810 815
Val Val Gln Arg Ala Cys Arg Ala Ile Leu His Ile Pro Arg Arg Ile
820 825 830
Arg Gln Gly Leu Glu Arg Ala Leu Leu
835 840
<210> 45
<211> 840
<212> PRT
<213> 人类免疫缺陷病毒
<400> 45
Met Arg Val Lys Gly Ile Arg Lys Asn Cys Gln His Leu Trp Arg Trp
1 5 10 15
Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys Ser Ala Ala Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Glu Thr Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Leu Leu Asn Ala Thr Asn Thr Asn Ser Thr Asn Met
130 135 140
Tyr Arg Trp Arg Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr
145 150 155 160
Ser Ile Arg Asp Lys Met Gln Lys Glu Tyr Ala Leu Phe Tyr Lys Leu
165 170 175
Asp Val Val Pro Ile Asp Asn Asn Thr Ser Tyr Arg Leu Ile Asn Cys
180 185 190
Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro
195 200 205
Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys Cys
210 215 220
Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr
225 230 235 240
Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu
245 250 255
Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu Asn
260 265 270
Phe Thr Asp Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Glu Ser Val
275 280 285
Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His
290 295 300
Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Glu Ile Ile Gly Asp
305 310 315 320
Ile Arg Gln Ala His Cys Asn Leu Ser Arg Ala Lys Trp Asn Asn Thr
325 330 335
Leu Lys Gln Val Val Thr Lys Leu Arg Glu Gln Phe Asp Asn Lys Thr
340 345 350
Ile Val Phe Asn Pro Ser Ser Gly Gly Asp Pro Glu Ile Val Met His
355 360 365
Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln Leu
370 375 380
Phe Asn Ser Thr Trp Asn Gly Thr Trp Asn Asn Thr Glu Gly Asn Ile
385 390 395 400
Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val
405 410 415
Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln Ile Arg Cys Ser
420 425 430
Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Glu
435 440 445
Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg
450 455 460
Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val
465 470 475 480
Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg Ala
485 490 495
Val Gly Ile Gly Ala Met Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser
500 505 510
Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
515 520 525
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
530 535 540
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
545 550 555 560
Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu
565 570 575
Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Thr Val
580 585 590
Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Asp Glu Ile Trp Asn
595 600 605
Asn Met Thr Trp Met Glu Trp Glu Arg Glu Ile Asp Asn Tyr Thr Gly
610 615 620
Leu Ile Tyr Thr Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
625 630 635 640
Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
645 650 655
Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile
660 665 670
Val Gly Gly Leu Val Gly Leu Arg Ile Val Phe Ala Val Leu Ser Ile
675 680 685
Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Arg
690 695 700
Leu Pro Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu
705 710 715 720
Gly Gly Glu Arg Asp Arg Asp Arg Ser Gly Arg Leu Val Asn Gly Phe
725 730 735
Leu Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr
740 745 750
His Arg Leu Arg Asp Leu Leu Leu Ile Val Ala Arg Ile Val Glu Leu
755 760 765
Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr Trp Trp Asn Leu Leu
770 775 780
Gln Tyr Trp Ser Gln Glu Leu Lys Asn Ser Ala Val Ser Leu Leu Asn
785 790 795 800
Ala Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile Glu Val
805 810 815
Val Gln Arg Ala Cys Arg Ala Ile Leu His Ile Pro Arg Arg Ile Arg
820 825 830
Gln Gly Leu Glu Arg Ala Leu Leu
835 840
<210> 46
<211> 835
<212> PRT
<213> 人类免疫缺陷病毒
<400> 46
Met Arg Val Arg Gly Ile Leu Arg Asn Cys Gln Gln Trp Trp Ile Trp
1 5 10 15
Gly Ile Leu Gly Phe Trp Met Leu Met Ile Cys Asn Val Val Gly Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Lys
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Glu Lys Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Val Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asp Met Val Asp Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asn Ala Thr Asn Ala Thr Asn Thr Met Gly Glu Ile Lys
130 135 140
Asn Cys Ser Phe Asn Ile Thr Thr Glu Leu Arg Asp Lys Lys Gln Lys
145 150 155 160
Val Tyr Ala Leu Phe Tyr Arg Leu Asp Ile Val Pro Leu Asn Glu Asn
165 170 175
Asn Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala
180 185 190
Cys Pro Lys Val Ser Phe Asp Pro Ile Pro Ile His Tyr Cys Ala Pro
195 200 205
Ala Gly Tyr Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr
210 215 220
Gly Pro Cys Asn Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys
225 230 235 240
Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu
245 250 255
Glu Ile Ile Ile Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Thr Ile
260 265 270
Ile Val His Leu Asn Glu Ser Val Glu Ile Val Cys Thr Arg Pro Asn
275 280 285
Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly Pro Gly Gln Thr Phe Tyr
290 295 300
Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile
305 310 315 320
Ser Glu Asp Lys Trp Asn Lys Thr Leu Gln Lys Val Ser Lys Lys Leu
325 330 335
Lys Glu His Phe Pro Asn Lys Thr Ile Lys Phe Glu Pro Ser Ser Gly
340 345 350
Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Arg Gly Glu Phe
355 360 365
Phe Tyr Cys Asn Thr Ser Lys Leu Phe Asn Ser Thr Tyr Asn Ser Thr
370 375 380
Asn Ser Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met
385 390 395 400
Trp Gln Glu Val Gly Arg Ala Met Tyr Ala Pro Pro Ile Ala Gly Asn
405 410 415
Ile Thr Cys Lys Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly
420 425 430
Gly Lys Asn Asn Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg
435 440 445
Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile Lys
450 455 460
Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Glu Arg
465 470 475 480
Glu Lys Arg Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu Gly
485 490 495
Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln
500 505 510
Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu
515 520 525
Arg Ala Ile Glu Ala Gln Gln His Met Leu Gln Leu Thr Val Trp Gly
530 535 540
Ile Lys Gln Leu Gln Thr Arg Val Leu Ala Ile Glu Arg Tyr Leu Lys
545 550 555 560
Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys
565 570 575
Thr Thr Ala Val Pro Trp Asn Ser Ser Trp Ser Asn Lys Ser Gln Glu
580 585 590
Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Asp Arg Glu Ile Ser
595 600 605
Asn Tyr Thr Asp Thr Ile Tyr Arg Leu Leu Glu Asp Ser Gln Asn Gln
610 615 620
Gln Glu Lys Asn Glu Lys Asp Leu Leu Ala Leu Asp Ser Trp Lys Asn
625 630 635 640
Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile
645 650 655
Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Ile Phe Ala
660 665 670
Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser
675 680 685
Phe Gln Thr Leu Thr Pro Asn Pro Arg Gly Pro Asp Arg Leu Gly Arg
690 695 700
Ile Glu Glu Glu Gly Gly Glu Gln Asp Arg Asp Arg Ser Ile Arg Leu
705 710 715 720
Val Ser Gly Phe Leu Ala Leu Ala Trp Asp Asp Leu Arg Ser Leu Cys
725 730 735
Leu Phe Ser Tyr His Arg Leu Arg Asp Phe Ile Leu Ile Ala Ala Arg
740 745 750
Ala Val Glu Leu Leu Gly Arg Ser Ser Leu Arg Gly Leu Gln Arg Gly
755 760 765
Trp Glu Ala Leu Lys Tyr Leu Gly Ser Leu Val Gln Tyr Trp Gly Leu
770 775 780
Glu Leu Lys Lys Ser Ala Ile Ser Leu Leu Asp Thr Ile Ala Ile Ala
785 790 795 800
Val Ala Glu Gly Thr Asp Arg Ile Ile Glu Leu Ile Gln Arg Ile Cys
805 810 815
Arg Ala Ile Arg Asn Ile Pro Arg Arg Ile Arg Gln Gly Phe Glu Ala
820 825 830
Ala Leu Gln
835
<210> 47
<211> 835
<212> PRT
<213> 人类免疫缺陷病毒
<400> 47
Met Arg Val Met Gly Ile Leu Arg Asn Cys Gln Gln Trp Trp Ile Trp
1 5 10 15
Gly Ile Leu Gly Phe Trp Met Leu Met Ile Cys Asn Val Val Gly Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Lys
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Glu Arg Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Met Val Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asp Met Val Asp Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asn Ala Thr Asn Ala Thr Asn Thr Met Gly Glu Met Lys
130 135 140
Asn Cys Ser Phe Asn Ile Thr Thr Glu Leu Arg Asp Lys Lys Gln Lys
145 150 155 160
Val Tyr Ala Leu Phe Tyr Arg Leu Asp Ile Val Pro Leu Asn Asp Asn
165 170 175
Asn Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala
180 185 190
Cys Pro Lys Val Ser Phe Asp Pro Ile Pro Ile His Tyr Cys Ala Pro
195 200 205
Ala Gly Tyr Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr
210 215 220
Gly Pro Cys Asn Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys
225 230 235 240
Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu
245 250 255
Glu Ile Ile Ile Arg Ser Glu Asn Leu Thr Asp Asn Ala Lys Thr Ile
260 265 270
Ile Val His Leu Asn Glu Ser Val Glu Ile Val Cys Thr Arg Pro Asn
275 280 285
Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly Pro Gly Gln Thr Phe Tyr
290 295 300
Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile
305 310 315 320
Ser Glu Glu Lys Trp Asn Lys Thr Leu Gln Arg Val Gly Glu Lys Leu
325 330 335
Lys Glu His Phe Pro Asn Lys Thr Ile Lys Phe Ala Pro Ser Ser Gly
340 345 350
Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Arg Gly Glu Phe
355 360 365
Phe Tyr Cys Asn Thr Ser Arg Leu Phe Asn Ser Thr Tyr Asn Ser Lys
370 375 380
Asn Ser Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met
385 390 395 400
Trp Gln Gly Val Gly Arg Ala Met Tyr Ala Pro Pro Ile Ala Gly Asn
405 410 415
Ile Thr Cys Lys Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly
420 425 430
Gly Lys Asn Asn Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg
435 440 445
Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile Lys
450 455 460
Pro Leu Gly Ile Ala Pro Thr Glu Ala Lys Arg Arg Val Val Glu Arg
465 470 475 480
Glu Lys Arg Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu Gly
485 490 495
Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln
500 505 510
Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu
515 520 525
Arg Ala Ile Glu Ala Gln Gln His Met Leu Gln Leu Thr Val Trp Gly
530 535 540
Ile Lys Gln Leu Gln Thr Arg Val Leu Ala Ile Glu Arg Tyr Leu Lys
545 550 555 560
Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys
565 570 575
Thr Thr Ala Val Pro Trp Asn Ser Ser Trp Ser Asn Lys Ser Gln Glu
580 585 590
Glu Ile Trp Asp Asn Met Thr Trp Met Gln Trp Asp Arg Glu Ile Ser
595 600 605
Asn Tyr Thr Asp Thr Ile Tyr Arg Leu Leu Glu Asp Ser Gln Asn Gln
610 615 620
Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Ser Trp Glu Asn
625 630 635 640
Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile
645 650 655
Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Ile Phe Ala
660 665 670
Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser
675 680 685
Phe Gln Thr Leu Thr Pro Asn Pro Arg Gly Pro Asp Arg Leu Gly Arg
690 695 700
Ile Glu Glu Glu Gly Gly Glu Gln Asp Arg Asp Arg Ser Ile Arg Leu
705 710 715 720
Val Ser Gly Phe Leu Ala Leu Ala Trp Asp Asp Leu Arg Ser Leu Cys
725 730 735
Leu Phe Ser Tyr His Arg Leu Arg Asp Phe Ile Leu Ile Ala Ala Arg
740 745 750
Ala Val Glu Leu Leu Gly Arg Ser Ser Leu Arg Gly Leu Gln Arg Gly
755 760 765
Trp Glu Ala Leu Lys Tyr Leu Gly Ser Leu Val Gln Tyr Trp Gly Leu
770 775 780
Glu Leu Lys Lys Ser Ala Ile Ser Leu Leu Asp Thr Ile Ala Ile Ala
785 790 795 800
Val Ala Glu Gly Thr Asp Arg Ile Ile Glu Leu Ile Gln Arg Ile Cys
805 810 815
Arg Ala Ile Arg Asn Ile Pro Arg Arg Ile Arg Gln Gly Phe Glu Ala
820 825 830
Ala Leu Leu
835
<210> 48
<211> 840
<212> PRT
<213> 人类免疫缺陷病毒
<400> 48
Met Arg Val Arg Gly Ile Gln Arg Asn Tyr Gln His Leu Trp Arg Trp
1 5 10 15
Gly Ile Met Leu Leu Gly Met Leu Met Ile Cys Ser Val Ala Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ser Tyr Lys Thr Glu Ala
50 55 60
His Asn Ile Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Glu Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Val Lys Arg Asn Asn Thr Ser Asn Asp Thr Asn Glu
130 135 140
Gly Glu Met Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Arg Asp
145 150 155 160
Lys Lys Lys Gln Val His Ala Leu Phe Tyr Lys Leu Asp Val Val Pro
165 170 175
Ile Asp Asp Asn Asn Ser Asn Thr Ser Tyr Arg Leu Ile Asn Cys Asn
180 185 190
Thr Ser Ala Ile Thr Gln Ala Cys Pro Lys Val Thr Phe Glu Pro Ile
195 200 205
Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys
210 215 220
Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val
225 230 235 240
Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu
245 250 255
Asn Gly Ser Leu Ala Glu Glu Glu Ile Ile Ile Arg Ser Glu Asn Leu
260 265 270
Thr Asn Asn Ala Lys Ile Ile Ile Val Gln Leu Asn Glu Ser Val Thr
275 280 285
Ile Asn Cys Thr Arg Pro Tyr Asn Asn Thr Arg Gln Arg Thr Pro Ile
290 295 300
Gly Pro Gly Gln Ala Leu Tyr Thr Thr Arg Ile Lys Gly Asp Ile Arg
305 310 315 320
Gln Ala His Cys Asn Ile Ser Arg Ala Glu Trp Asn Lys Thr Leu Gln
325 330 335
Gln Val Ala Lys Lys Leu Gly Asp Leu Leu Asn Lys Thr Thr Ile Ile
340 345 350
Phe Lys Pro Ser Ser Gly Gly Asp Pro Glu Ile Thr Thr His Ser Phe
355 360 365
Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Arg Leu Phe Asn
370 375 380
Ser Thr Trp Asn Asn Thr Lys Trp Asn Ser Thr Gly Lys Ile Thr Leu
385 390 395 400
Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Gly Val Gly Lys
405 410 415
Ala Met Tyr Ala Pro Pro Ile Glu Gly Leu Ile Lys Cys Ser Ser Asn
420 425 430
Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Ala Asn Asn Ser His
435 440 445
Asn Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg
450 455 460
Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val
465 470 475 480
Ala Pro Thr Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala
485 490 495
Ile Gly Leu Gly Ala Met Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser
500 505 510
Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
515 520 525
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
530 535 540
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
545 550 555 560
Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu
565 570 575
Leu Gly Ile Trp Gly Cys Ser Gly Lys His Ile Cys Thr Thr Thr Val
580 585 590
Pro Trp Asn Ser Ser Trp Ser Asn Lys Ser Leu Asp Glu Ile Trp Asn
595 600 605
Asn Met Thr Trp Met Glu Trp Glu Arg Glu Ile Asp Asn Tyr Thr Gly
610 615 620
Leu Ile Tyr Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
625 630 635 640
Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
645 650 655
Phe Ser Ile Thr Gln Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile
660 665 670
Val Gly Gly Leu Ile Gly Leu Arg Ile Val Phe Ala Val Leu Ser Leu
675 680 685
Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu
690 695 700
Leu Pro Ala Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu
705 710 715 720
Gly Gly Glu Gln Gly Arg Gly Arg Ser Ile Arg Leu Val Asn Gly Phe
725 730 735
Ser Ala Leu Ile Trp Asp Asp Leu Arg Asn Leu Cys Leu Phe Ser Tyr
740 745 750
His Arg Leu Arg Asp Leu Ile Leu Ile Ala Ala Arg Ile Val Glu Leu
755 760 765
Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr Leu Trp Asn Leu Leu
770 775 780
Gln Tyr Trp Ile Gln Glu Leu Lys Asn Ser Ala Ile Ser Leu Phe Asp
785 790 795 800
Thr Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Val Ile Glu Ile
805 810 815
Val Gln Arg Ala Cys Arg Ala Ile Leu Asn Ile Pro Thr Arg Ile Arg
820 825 830
Gln Gly Leu Glu Arg Ala Leu Leu
835 840
<210> 49
<211> 832
<212> PRT
<213> 人类免疫缺陷病毒
<400> 49
Met Arg Val Arg Gly Met Gln Arg Asn Trp Gln His Leu Gly Lys Trp
1 5 10 15
Gly Leu Leu Phe Leu Gly Ile Leu Ile Ile Cys Asn Ala Ala Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ser Tyr Glu Lys Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn Phe Asp Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Thr Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Val Asn Ala Thr Asn Asn Asp Thr Asn Asp Asn Lys
130 135 140
Thr Gly Ala Ile Gln Asn Cys Ser Phe Asn Met Thr Thr Glu Val Arg
145 150 155 160
Asp Lys Lys Leu Lys Val His Ala Leu Phe Tyr Lys Leu Asp Ile Val
165 170 175
Pro Ile Ser Asn Asn Asn Ser Lys Tyr Arg Leu Ile Asn Cys Asn Thr
180 185 190
Ser Thr Ile Thr Gln Ala Cys Pro Lys Val Ser Trp Asp Pro Ile Pro
195 200 205
Ile His Tyr Cys Ala Pro Ala Gly Tyr Ala Ile Leu Lys Cys Asn Asp
210 215 220
Lys Arg Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln
225 230 235 240
Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn
245 250 255
Gly Ser Leu Ala Glu Glu Asp Ile Ile Ile Arg Ser Gln Asn Ile Ser
260 265 270
Asp Asn Ala Lys Thr Ile Ile Val His Leu Asn Glu Ser Val Gln Ile
275 280 285
Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His Leu Gly
290 295 300
Pro Gly Gln Ala Phe Tyr Ala Thr Gly Glu Ile Ile Gly Asp Ile Arg
305 310 315 320
Lys Ala His Cys Asn Ile Ser Gly Thr Gln Trp Asn Lys Thr Leu Glu
325 330 335
Gln Val Lys Ala Lys Leu Lys Ser His Phe Pro Asn Lys Thr Ile Lys
340 345 350
Phe Asn Ser Ser Ser Gly Gly Asp Leu Glu Ile Thr Met His Ser Phe
355 360 365
Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn
370 375 380
Asp Thr Gly Ser Asn Gly Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln
385 390 395 400
Ile Val Asn Met Trp Gln Glu Val Gly Arg Ala Met Tyr Ala Ala Pro
405 410 415
Ile Ala Gly Asn Ile Thr Cys Asn Ser Asn Ile Thr Gly Leu Leu Leu
420 425 430
Thr Arg Asp Gly Gly Gln Asn Asn Thr Glu Thr Phe Arg Pro Gly Gly
435 440 445
Gly Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val
450 455 460
Val Glu Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Gln
465 470 475 480
Val Val Lys Arg Glu Arg Arg Ala Val Gly Ile Gly Ala Val Phe Leu
485 490 495
Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr
500 505 510
Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln
515 520 525
Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu
530 535 540
Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu
545 550 555 560
Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Leu Trp Gly Cys Ser Gly
565 570 575
Lys Leu Ile Cys Thr Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn
580 585 590
Lys Ser Gln Asp Glu Ile Trp Asn Asn Met Thr Trp Met Glu Trp Glu
595 600 605
Lys Glu Ile Ser Asn Tyr Ser Asn Ile Ile Tyr Arg Leu Ile Glu Glu
610 615 620
Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Ala Leu Asp
625 630 635 640
Lys Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile Ser Asn Trp Leu Trp
645 650 655
Tyr Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg
660 665 670
Ile Val Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg Lys Gly Tyr
675 680 685
Ser Pro Leu Ser Leu Gln Thr Leu Ile Pro Ser Pro Arg Glu Pro Asp
690 695 700
Arg Pro Glu Gly Ile Glu Glu Gly Gly Gly Glu Gln Gly Lys Asp Arg
705 710 715 720
Ser Val Arg Leu Val Asn Gly Phe Leu Ala Leu Val Trp Asp Asp Leu
725 730 735
Arg Asn Leu Cys Leu Phe Ser Tyr Arg His Leu Arg Asp Phe Ile Leu
740 745 750
Ile Ala Ala Arg Ile Val Asp Arg Gly Leu Arg Arg Gly Trp Glu Ala
755 760 765
Leu Lys Tyr Leu Gly Asn Leu Thr Gln Tyr Trp Ser Gln Glu Leu Lys
770 775 780
Asn Ser Ala Ile Ser Leu Leu Asn Thr Thr Ala Ile Val Val Ala Glu
785 790 795 800
Gly Thr Asp Arg Val Ile Glu Ala Leu Gln Arg Ala Gly Arg Ala Val
805 810 815
Leu Asn Ile Pro Arg Arg Ile Arg Gln Gly Leu Glu Arg Ala Leu Leu
820 825 830
<210> 50
<211> 831
<212> PRT
<213> 人类免疫缺陷病毒
<400> 50
Met Arg Val Arg Glu Met Gln Arg Asn Trp Gln His Leu Gly Lys Trp
1 5 10 15
Gly Leu Leu Phe Leu Gly Ile Leu Ile Ile Cys Asn Ala Ala Asp Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Glu Arg Glu Val
50 55 60
His Asn Val Trp Ala Thr Tyr Ala Cys Val Pro Thr Asp Pro Ser Pro
65 70 75 80
Gln Glu Leu Val Leu Gly Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Asp Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Val Asn Val Thr Ile Asn Thr Thr Asn Val Thr Leu
130 135 140
Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Lys Asp
145 150 155 160
Lys Lys Lys Lys Glu Tyr Ala Leu Phe Tyr Arg Leu Asp Val Val Pro
165 170 175
Ile Asn Asn Ser Ile Val Tyr Arg Leu Ile Ser Cys Asn Thr Ser Thr
180 185 190
Val Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His
195 200 205
Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys
210 215 220
Phe Asn Gly Thr Gly Leu Cys Arg Asn Val Ser Thr Val Gln Cys Thr
225 230 235 240
His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser
245 250 255
Leu Ala Glu Glu Asp Ile Ile Ile Arg Ser Glu Asn Ile Ser Asp Asn
260 265 270
Thr Lys Thr Ile Ile Val Gln Phe Asn Arg Ser Val Glu Ile Asn Cys
275 280 285
Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly Pro Gly
290 295 300
Arg Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Lys Ala
305 310 315 320
Tyr Cys Asn Ile Asn Arg Thr Leu Trp Asn Glu Thr Leu Lys Lys Val
325 330 335
Ala Glu Glu Phe Lys Asn His Phe Asn Ile Thr Val Thr Phe Asn Pro
340 345 350
Ser Ser Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Arg
355 360 365
Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn Asn Thr Glu
370 375 380
Val Asn Asn Thr Lys Thr Ile Thr Leu Pro Cys Arg Ile Arg Gln Phe
385 390 395 400
Val Asn Met Trp Gln Arg Val Gly Arg Ala Met Tyr Ala Pro Pro Ile
405 410 415
Ala Gly Gln Ile Gln Cys Asn Ser Asn Ile Thr Gly Leu Leu Leu Thr
420 425 430
Arg Asp Gly Gly Lys Asn Gly Ser Glu Thr Leu Arg Pro Gly Gly Gly
435 440 445
Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val
450 455 460
Lys Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Gln Val
465 470 475 480
Val Gln Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Val Leu Leu Gly
485 490 495
Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu
500 505 510
Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser
515 520 525
Asn Leu Leu Lys Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
530 535 540
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu Arg
545 550 555 560
Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
565 570 575
Leu Ile Cys Thr Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Lys
580 585 590
Ser Gln Asp Glu Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Lys
595 600 605
Glu Ile Ser Asn Tyr Thr Asp Thr Ile Tyr Arg Leu Ile Glu Asp Ala
610 615 620
Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys
625 630 635 640
Trp Asp Asn Leu Trp Ser Trp Phe Thr Ile Thr Asn Trp Leu Trp Tyr
645 650 655
Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile
660 665 670
Val Phe Ala Val Leu Ser Val Val Asn Arg Val Arg Gln Gly Tyr Ser
675 680 685
Pro Leu Ser Leu Gln Thr Leu Ile Pro Asn Pro Arg Gly Pro Glu Arg
690 695 700
Pro Gly Gly Ile Glu Glu Glu Gly Gly Glu Gln Asp Arg Asp Arg Ser
705 710 715 720
Ile Arg Leu Val Ser Gly Phe Leu Ala Leu Ala Trp Asp Asp Leu Arg
725 730 735
Ser Leu Cys Leu Phe Ser Tyr Arg His Leu Arg Asp Phe Ile Leu Ile
740 745 750
Ala Ala Arg Thr Val Asp Met Gly Leu Lys Arg Gly Trp Glu Ala Leu
755 760 765
Lys Tyr Leu Trp Asn Leu Pro Gln Tyr Trp Gly Gln Glu Leu Lys Asn
770 775 780
Ser Ala Ile Ser Leu Leu Asp Thr Thr Ala Ile Ala Val Ala Glu Gly
785 790 795 800
Thr Asp Arg Ile Ile Glu Val Leu Gln Arg Ala Gly Arg Ala Val Leu
805 810 815
His Ile Pro Arg Arg Ile Arg Gln Gly Phe Glu Arg Ala Leu Leu
820 825 830
<210> 51
<211> 842
<212> PRT
<213> 人类免疫缺陷病毒
<400> 51
Met Arg Val Lys Gly Ile Gln Arg Asn Trp Gln His Leu Trp Lys Trp
1 5 10 15
Gly Thr Leu Ile Leu Gly Leu Val Ile Ile Cys Ser Ala Ser Asn Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Glu Asp Ala Asp
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Ser Thr Glu Arg
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Thr Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Glu Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Val Asn Val Thr Asn Asn Asn Thr Asn Asn Thr Lys
130 135 140
Lys Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Arg Asp
145 150 155 160
Lys Lys Lys Lys Glu Tyr Ala Leu Phe Tyr Arg Leu Asp Val Val Pro
165 170 175
Ile Asn Asp Asn Gly Asn Ser Ser Ile Tyr Arg Leu Ile Asn Cys Asn
180 185 190
Val Ser Thr Ile Lys Gln Ala Cys Pro Lys Val Thr Phe Asp Pro Ile
195 200 205
Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Arg
210 215 220
Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val
225 230 235 240
Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu
245 250 255
Asn Gly Ser Leu Ala Glu Glu Glu Ile Ile Ile Arg Ser Glu Asn Ile
260 265 270
Thr Asp Asn Thr Lys Val Ile Ile Val Gln Leu Asn Glu Thr Ile Glu
275 280 285
Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile
290 295 300
Gly Pro Gly Gln Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile
305 310 315 320
Arg Gln Ala His Cys Asn Val Ser Arg Thr Lys Trp Asn Glu Met Leu
325 330 335
Gln Lys Val Lys Ala Gln Leu Lys Lys Ile Phe Asn Lys Ser Ile Thr
340 345 350
Phe Asn Ser Ser Ser Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe
355 360 365
Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn
370 375 380
Asn Ser Leu Leu Asn Ser Thr Asn Ser Thr Ile Thr Leu Pro Cys Lys
385 390 395 400
Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly Gln Ala Met Tyr
405 410 415
Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Arg Ser Asn Ile Thr Gly
420 425 430
Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Asn Thr Glu Thr Phe Arg
435 440 445
Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys
450 455 460
Tyr Lys Ile Val Lys Ile Lys Pro Leu Gly Val Ala Pro Thr Arg Ala
465 470 475 480
Arg Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val Gly Leu Gly Ala
485 490 495
Val Leu Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala
500 505 510
Ser Ile Thr Leu Thr Val Gln Val Arg Gln Leu Leu Ser Gly Ile Val
515 520 525
Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu
530 535 540
Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu
545 550 555 560
Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly
565 570 575
Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro Trp Asn Thr Ser
580 585 590
Trp Ser Asn Lys Ser Tyr Asn Glu Ile Trp Asp Asn Met Thr Trp Ile
595 600 605
Glu Trp Glu Arg Glu Ile Ser Asn Tyr Thr Gln Gln Ile Tyr Ser Leu
610 615 620
Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu
625 630 635 640
Ala Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile Thr Lys
645 650 655
Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Ile
660 665 670
Gly Leu Arg Ile Val Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg
675 680 685
Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu Thr His His Gln Arg
690 695 700
Glu Pro Asp Arg Pro Glu Arg Ile Glu Glu Gly Gly Gly Glu Gln Asp
705 710 715 720
Lys Asp Arg Ser Ile Arg Leu Val Ser Gly Phe Leu Ala Leu Ala Trp
725 730 735
Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg Leu Arg Asp
740 745 750
Phe Ile Leu Ile Ala Ala Arg Thr Val Glu Leu Leu Gly Arg Ser Ser
755 760 765
Leu Lys Gly Leu Arg Leu Gly Trp Glu Gly Leu Lys Tyr Leu Trp Asn
770 775 780
Leu Leu Leu Tyr Trp Gly Gln Glu Leu Lys Asn Ser Ala Ile Asn Leu
785 790 795 800
Leu Asp Thr Ile Ala Ile Ala Val Ala Asn Trp Thr Asp Arg Val Ile
805 810 815
Glu Val Ala Gln Arg Ala Cys Arg Ala Ile Leu Asn Ile Pro Arg Arg
820 825 830
Ile Arg Gln Gly Leu Glu Arg Ala Leu Leu
835 840
<210> 52
<211> 839
<212> PRT
<213> 人类免疫缺陷病毒
<400> 52
Thr Arg Val Met Glu Thr Gln Arg Asn Tyr Pro Ser Leu Trp Arg Trp
1 5 10 15
Gly Thr Leu Ile Leu Gly Met Leu Leu Ile Cys Ser Ala Ala Gly Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Lys
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Glu Thr Glu Lys
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Met Val Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Glu
85 90 95
Asn Asp Met Val Glu Gln Met His Thr Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asp Cys Ser Asn Val Asn Thr Thr Asn Ala Thr Asn Ser Arg Phe Asn
130 135 140
Met Gln Glu Glu Leu Thr Asn Cys Ser Phe Asn Val Thr Thr Val Ile
145 150 155 160
Arg Asp Lys Gln Gln Lys Val His Ala Leu Phe Tyr Arg Leu Asp Val
165 170 175
Val Pro Ile Asp Asp Asn Asn Ser Tyr Gln Tyr Arg Leu Ile Asn Cys
180 185 190
Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro
195 200 205
Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys
210 215 220
Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr
225 230 235 240
Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu
245 250 255
Leu Asn Gly Ser Leu Ala Glu Glu Gln Val Ile Ile Arg Ser Lys Asn
260 265 270
Ile Ser Asp Asn Thr Lys Asn Ile Ile Val Gln Leu Asn Lys Pro Val
275 280 285
Glu Ile Thr Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His
290 295 300
Leu Gly Pro Gly Gln Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp
305 310 315 320
Ile Arg Gln Ala His Cys Asn Ile Ser Gly Lys Lys Trp Asn Lys Thr
325 330 335
Leu His Gln Val Val Thr Gln Leu Gly Lys Tyr Phe Asp Asn Arg Thr
340 345 350
Ile Ile Phe Lys Pro His Ser Gly Gly Asp Met Glu Val Thr Thr His
355 360 365
Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu
370 375 380
Phe Asn Ser Ser Trp Thr Asn Ser Thr Asn Asp Thr Lys Asn Ile Ile
385 390 395 400
Thr Leu Pro Cys Arg Ile Lys Gln Ile Val Asn Met Trp Gln Arg Val
405 410 415
Gly Gln Ala Met Tyr Ala Pro Pro Ile Lys Gly Asn Ile Thr Cys Val
420 425 430
Ser Asn Ile Thr Gly Leu Ile Leu Thr Phe Asp Glu Gly Asn Asn Thr
435 440 445
Val Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser
450 455 460
Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala
465 470 475 480
Pro Thr Glu Ala Arg Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val
485 490 495
Gly Met Gly Ala Phe Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr
500 505 510
Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu
515 520 525
Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Gln Ala
530 535 540
Gln Gln His Met Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln
545 550 555 560
Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu
565 570 575
Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro
580 585 590
Trp Asn Ser Ser Trp Ser Asn Lys Ser Leu Asp Glu Ile Trp Asp Asn
595 600 605
Met Thr Trp Met Glu Trp Asp Lys Gln Ile Asn Asn Tyr Thr Glu Glu
610 615 620
Ile Tyr Arg Leu Leu Glu Val Ser Gln Thr Gln Gln Glu Lys Asn Glu
625 630 635 640
Gln Asp Leu Leu Ala Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe
645 650 655
Ser Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val
660 665 670
Gly Gly Leu Ile Gly Leu Arg Ile Ile Phe Ala Val Leu Ser Ile Val
675 680 685
Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu Ile
690 695 700
Pro Asn Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu Gly
705 710 715 720
Gly Glu Gln Asp Arg Asp Arg Ser Val Arg Leu Val Asn Gly Phe Leu
725 730 735
Pro Leu Val Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr Arg
740 745 750
Leu Leu Arg Asp Leu Leu Leu Ile Val Val Arg Thr Val Glu Leu Leu
755 760 765
Gly Arg Arg Gly Arg Glu Ala Leu Lys Tyr Leu Trp Asn Leu Leu Gln
770 775 780
Tyr Trp Gly Gln Glu Leu Lys Asn Ser Ala Ile Asn Leu Leu Asn Thr
785 790 795 800
Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Ile Ile Glu Ile Val
805 810 815
Gln Arg Ala Trp Arg Ala Ile Leu His Ile Pro Arg Arg Ile Arg Gln
820 825 830
Gly Phe Glu Arg Thr Leu Leu
835
<210> 53
<211> 854
<212> PRT
<213> 人类免疫缺陷病毒
<400> 53
Met Arg Val Lys Glu Thr Gln Met Asn Trp Pro Asn Leu Trp Lys Trp
1 5 10 15
Gly Thr Leu Ile Leu Gly Leu Val Ile Ile Cys Ser Ala Ser Asp Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Arg Asp Ala Asp
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala His Glu Thr Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile His Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met Gln Glu Asp Val Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asn Ala Asn Leu Thr Asn Val Asn Asn Ile Thr Asn Val
130 135 140
Ser Asn Ile Ile Gly Asn Ile Thr Asn Glu Val Arg Asn Cys Ser Phe
145 150 155 160
Asn Met Thr Thr Glu Leu Arg Asp Lys Lys Gln Lys Val His Ala Leu
165 170 175
Phe Tyr Lys Leu Asp Ile Val Gln Ile Glu Asp Asn Asn Ser Tyr Arg
180 185 190
Leu Ile Asn Cys Asn Thr Ser Val Ile Lys Gln Ala Cys Pro Lys Ile
195 200 205
Ser Phe Asp Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Tyr Ala
210 215 220
Ile Leu Lys Cys Asn Asp Lys Asn Phe Asn Gly Thr Gly Pro Cys Lys
225 230 235 240
Asn Val Ser Ser Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser
245 250 255
Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Ile Ile
260 265 270
Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Thr Ile Ile Val His Leu
275 280 285
Asn Lys Ser Val Glu Ile Asn Cys Thr Arg Pro Ser Asn Asn Thr Arg
290 295 300
Thr Ser Ile Thr Ile Gly Pro Gly Gln Val Phe Tyr Arg Thr Gly Asp
305 310 315 320
Ile Ile Gly Asp Ile Arg Lys Ala Tyr Cys Glu Ile Asn Gly Thr Lys
325 330 335
Trp Asn Glu Val Leu Lys Gln Val Thr Glu Lys Leu Lys Glu His Phe
340 345 350
Asn Asn Lys Thr Ile Ile Phe Gln Pro Pro Ser Gly Gly Asp Leu Glu
355 360 365
Ile Thr Met His His Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn
370 375 380
Thr Thr Lys Leu Phe Asn Asn Thr Cys Ile Gly Asn Glu Thr Met Glu
385 390 395 400
Gly Cys Asn Gly Thr Ile Ile Leu Pro Cys Lys Ile Lys Gln Ile Ile
405 410 415
Asn Met Trp Gln Gly Ala Gly Gln Ala Met Tyr Ala Pro Pro Ile Ser
420 425 430
Gly Arg Ile Asn Cys Val Ser Asn Ile Thr Gly Ile Leu Leu Thr Arg
435 440 445
Asp Gly Gly Ala Asn Asn Thr Asn Glu Thr Phe Arg Pro Gly Gly Gly
450 455 460
Asn Ile Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val
465 470 475 480
Gln Ile Glu Pro Leu Gly Ile Ala Pro Thr Arg Ala Lys Arg Arg Val
485 490 495
Val Glu Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Met Ile Phe Gly
500 505 510
Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu
515 520 525
Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser
530 535 540
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
545 550 555 560
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
565 570 575
Tyr Leu Lys Asp Gln Lys Phe Leu Gly Leu Trp Gly Cys Ser Gly Lys
580 585 590
Ile Ile Cys Thr Thr Ala Val Pro Trp Asn Ser Thr Trp Ser Asn Arg
595 600 605
Ser Phe Glu Glu Ile Trp Asn Asn Met Thr Trp Ile Glu Trp Glu Arg
610 615 620
Glu Ile Ser Asn Tyr Thr Asn Gln Ile Tyr Glu Ile Leu Thr Glu Ser
625 630 635 640
Gln Asn Gln Gln Asp Arg Asn Glu Lys Asp Leu Leu Glu Leu Asp Lys
645 650 655
Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr
660 665 670
Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile
675 680 685
Ile Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser
690 695 700
Pro Leu Ser Phe Gln Thr Pro Thr His His Gln Arg Glu Pro Asp Arg
705 710 715 720
Pro Glu Arg Ile Glu Glu Gly Gly Gly Glu Gln Gly Arg Asp Arg Ser
725 730 735
Val Arg Leu Val Ser Gly Phe Leu Ala Leu Ala Trp Asp Asp Leu Arg
740 745 750
Ser Leu Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Phe Ile Leu Ile
755 760 765
Ala Ala Arg Thr Val Glu Leu Leu Gly His Ser Ser Leu Lys Gly Leu
770 775 780
Arg Arg Gly Trp Glu Gly Leu Lys Tyr Leu Gly Asn Leu Leu Leu Tyr
785 790 795 800
Trp Gly Gln Glu Leu Lys Ile Ser Ala Ile Ser Leu Leu Asp Ala Thr
805 810 815
Ala Ile Ala Val Ala Gly Trp Thr Asp Arg Val Ile Glu Val Ala Gln
820 825 830
Gly Ala Trp Arg Ala Ile Leu His Ile Pro Arg Arg Ile Arg Gln Gly
835 840 845
Leu Glu Arg Ala Leu Leu
850
<210> 54
<211> 844
<212> PRT
<213> 人类免疫缺陷病毒1型
<400> 54
Met Arg Val Met Gly Ile Gln Lys Asn Tyr Pro Leu Leu Trp Arg Trp
1 5 10 15
Gly Met Ile Ile Phe Trp Ile Met Ile Ile Cys Asn Ala Glu Asn Leu
20 25 30
Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Arg Asp Ala Glu Thr
35 40 45
Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val His
50 55 60
Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro Gln
65 70 75 80
Glu Ile His Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn
85 90 95
Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp Gln
100 105 110
Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu Asp
115 120 125
Cys His Asn Asn Ile Thr Asn Ser Asn Thr Thr Asn Asn Asn Ala Gly
130 135 140
Glu Ile Lys Asn Cys Ser Phe Asn Met Thr Thr Glu Leu Arg Asp Lys
145 150 155 160
Lys Gln Lys Val Tyr Ala Leu Phe Tyr Arg Leu Asp Val Val Gln Ile
165 170 175
Asn Lys Asn Asn Ser Gln Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala
180 185 190
Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His
195 200 205
Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Glu
210 215 220
Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr
225 230 235 240
His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser
245 250 255
Leu Ala Glu Glu Glu Ile Val Ile Arg Ser Glu Asn Ile Thr Asn Asn
260 265 270
Ala Lys Thr Ile Ile Val Gln Leu Val Lys Pro Val Lys Ile Asn Cys
275 280 285
Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Val Arg Ile Gly Pro Gly
290 295 300
Gln Thr Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala
305 310 315 320
His Cys Asn Val Ser Arg Thr Lys Trp Asn Asn Thr Leu Gln Gln Val
325 330 335
Ala Thr Gln Leu Arg Lys Tyr Phe Asn Lys Thr Ile Ile Phe Ala Asn
340 345 350
Pro Ser Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Gly
355 360 365
Gly Glu Phe Phe Tyr Cys Asn Thr Ser Glu Leu Phe Asn Ser Thr Trp
370 375 380
Asn Ser Thr Trp Asn Asn Thr Glu Lys Cys Ile Thr Leu Gln Cys Arg
385 390 395 400
Ile Lys Gln Ile Val Asn Met Trp Gln Lys Val Gly Gln Ala Met Tyr
405 410 415
Ala Pro Pro Ile Gln Gly Val Ile Arg Cys Glu Ser Asn Ile Thr Gly
420 425 430
Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Asn Ser Thr Asn Glu Thr
435 440 445
Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu
450 455 460
Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala Pro Thr
465 470 475 480
Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val Gly Leu
485 490 495
Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly
500 505 510
Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly
515 520 525
Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln
530 535 540
His Leu Leu Lys Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg
545 550 555 560
Val Leu Ala Leu Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile
565 570 575
Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Thr Val Pro Trp Asn
580 585 590
Ser Ser Trp Ser Asn Lys Thr Tyr Asn Asp Ile Trp Asp Asn Met Thr
595 600 605
Trp Leu Gln Trp Asp Lys Glu Ile Ser Asn Tyr Thr Asp Ile Ile Tyr
610 615 620
Asn Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp
625 630 635 640
Leu Leu Ala Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile
645 650 655
Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val Gly Gly
660 665 670
Leu Ile Gly Leu Arg Ile Val Phe Ala Val Leu Thr Ile Ile Asn Arg
675 680 685
Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu Thr His His
690 695 700
Gln Arg Glu Pro Asp Arg Pro Glu Arg Ile Glu Glu Gly Gly Gly Glu
705 710 715 720
Gln Asp Arg Asp Arg Ser Val Arg Leu Val Ser Gly Phe Leu Ala Leu
725 730 735
Ala Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg Leu
740 745 750
Arg Asp Phe Val Leu Ile Ala Ala Arg Thr Val Glu Leu Leu Gly His
755 760 765
Ser Ser Leu Lys Gly Leu Arg Leu Gly Trp Glu Ala Leu Lys Tyr Leu
770 775 780
Gly Asn Leu Leu Ser Tyr Trp Gly Gln Glu Leu Lys Asn Ser Ala Ile
785 790 795 800
Asn Leu Leu Asp Thr Ile Ala Ile Ala Val Ala Asn Trp Thr Asp Arg
805 810 815
Val Ile Glu Ile Gly Gln Arg Ala Gly Arg Ala Ile Leu Asn Ile Pro
820 825 830
Arg Arg Ile Arg Gln Gly Leu Glu Arg Ala Leu Leu
835 840
<210> 55
<211> 840
<212> PRT
<213> 人类免疫缺陷病毒
<400> 55
Met Arg Val Lys Glu Ile Arg Lys His Leu Trp Arg Trp Gly Thr Leu
1 5 10 15
Phe Leu Gly Met Leu Met Ile Cys Ser Ala Thr Glu Asn Leu Trp Val
20 25 30
Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr Thr Thr Leu
35 40 45
Phe Cys Ala Ser Asp Ala Lys Ala Tyr Ser Lys Glu Val His Asn Val
50 55 60
Trp Ala Thr Tyr Ala Cys Val Pro Thr Asp Pro Ser Pro Gln Glu Ile
65 70 75 80
Pro Leu Glu Asn Val Thr Glu Asn Phe Asn Met Gly Lys Asn Asn Met
85 90 95
Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp Gln Ser Leu
100 105 110
Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu Asn Cys Thr
115 120 125
Asp Leu Lys Lys Asn Val Thr Ser Thr Asn Thr Ser Ser Ile Lys Met
130 135 140
Met Glu Met Lys Asn Cys Ser Phe Asn Ile Thr Thr Asp Leu Arg Asp
145 150 155 160
Lys Val Lys Lys Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Gln
165 170 175
Ile Asp Asn Asp Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Val
180 185 190
Thr Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr
195 200 205
Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe
210 215 220
Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His
225 230 235 240
Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu
245 250 255
Ala Glu Glu Glu Val Val Ile Arg Ser Val Asn Phe Thr Asp Asn Thr
260 265 270
Lys Thr Ile Ile Val Gln Leu Lys Glu Pro Val Glu Ile Asn Cys Thr
275 280 285
Arg Pro Asn Asn Asn Thr Arg Lys Gly Ile His Ile Gly Pro Gly Arg
290 295 300
Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His
305 310 315 320
Cys Asn Ile Ser Ile Thr Lys Trp Asn Asn Thr Leu Lys Gln Ile Val
325 330 335
Ile Lys Leu Arg Lys Gln Phe Gly Asn Lys Thr Ile Val Phe Asn Gln
340 345 350
Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Gly
355 360 365
Gly Glu Phe Phe Tyr Cys Asn Thr Thr Lys Leu Phe Asn Ser Thr Trp
370 375 380
Asn Gly Thr Glu Glu Leu Asn Asn Thr Glu Gly Asp Ile Val Thr Leu
385 390 395 400
Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys
405 410 415
Ala Met Tyr Ala Pro Pro Ile Ala Gly Gln Ile Arg Cys Ser Ser Asn
420 425 430
Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Gln Ser Asn Val
435 440 445
Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg
450 455 460
Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val
465 470 475 480
Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg Ala
485 490 495
Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser
500 505 510
Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu
515 520 525
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
530 535 540
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
545 550 555 560
Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu
565 570 575
Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val
580 585 590
Pro Trp Asn Thr Ser Trp Ser Asn Lys Ser Leu Asp Glu Ile Trp Asn
595 600 605
Asn Met Thr Trp Met Glu Trp Glu Arg Glu Ile Asn Asn Tyr Thr Gly
610 615 620
Leu Ile Tyr Asn Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
625 630 635 640
Glu Gln Glu Ile Leu Ala Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
645 650 655
Phe Asp Ile Ser Lys Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile
660 665 670
Val Gly Gly Leu Val Gly Leu Arg Ile Ile Phe Ala Val Leu Ser Ile
675 680 685
Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Arg
690 695 700
Leu Pro Thr Gln Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu
705 710 715 720
Gly Gly Glu Arg Asp Arg Asp Thr Ser Ile Arg Leu Val Asn Gly Phe
725 730 735
Leu Ala Leu Ile Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ile Tyr
740 745 750
His His Leu Arg Asp Leu Leu Leu Ile Ala Ala Arg Ile Val Glu Leu
755 760 765
Leu Gly Arg Arg Gly Trp Glu Ala Leu Lys Tyr Trp Trp Asn Leu Leu
770 775 780
Gln Tyr Trp Ile Gln Glu Leu Lys Ser Ser Ala Ile Asn Leu Ile Asp
785 790 795 800
Thr Ile Ala Ile Ala Val Ala Gly Trp Thr Asp Arg Val Ile Glu Ile
805 810 815
Gly Gln Arg Phe Cys Arg Ala Ile Arg Asn Ile Pro Arg Arg Ile Arg
820 825 830
Gln Gly Ala Glu Lys Ala Leu Gln
835 840
<210> 56
<211> 848
<212> PRT
<213> 人类免疫缺陷病毒
<400> 56
Met Arg Val Met Gly Ile Gln Arg Asn Tyr Pro His Leu Trp Glu Trp
1 5 10 15
Gly Thr Leu Ile Leu Gly Leu Val Ile Ile Cys Ser Ala Ser Lys Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Arg Asp Ala Glu
35 40 45
Thr Thr Pro Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Lys Glu Val
50 55 60
His Asn Ile Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Ala Leu Lys Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Glu Gly Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Ala Leu
115 120 125
Asn Cys Ser Asn Ala Thr Ile Asn Asn Ser Thr Lys Thr Asn Ser Thr
130 135 140
Glu Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Arg Asp
145 150 155 160
Lys Lys Lys Lys Glu Tyr Ala Leu Phe Tyr Arg Leu Asp Ile Val Pro
165 170 175
Ile Asn Asp Ser Ala Asn Asn Asn Ser Ile Asn Ser Glu Tyr Met Leu
180 185 190
Ile Asn Cys Asn Ala Ser Thr Ile Lys Gln Ala Cys Pro Lys Val Thr
195 200 205
Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile
210 215 220
Leu Lys Cys Asn Asp Lys Asn Phe Thr Gly Leu Gly Pro Cys Thr Asn
225 230 235 240
Val Ser Ser Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr
245 250 255
Gln Leu Leu Leu Asn Gly Ser Leu Ala Thr Glu Gly Val Val Ile Arg
260 265 270
Ser Lys Asn Phe Thr Asp Asn Thr Lys Asn Ile Ile Val Gln Leu Ala
275 280 285
Lys Ala Val Lys Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys
290 295 300
Ser Val His Ile Gly Pro Gly Gln Thr Trp Tyr Ala Thr Gly Glu Ile
305 310 315 320
Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Gly Asn Asp Trp
325 330 335
Asn Glu Thr Leu Gln Lys Ile Val Glu Glu Leu Arg Lys His Phe Pro
340 345 350
Asn Lys Thr Ile Ile Phe Ala Pro Ser Ala Gly Gly Asp Leu Glu Ile
355 360 365
Thr Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr
370 375 380
Ser Glu Leu Phe Asn Ser Thr Tyr Met Asn Ser Thr Asn Ser Thr Thr
385 390 395 400
Ile Asn Lys Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val Ser
405 410 415
Met Trp Gln Glu Val Gly Gln Ala Met Tyr Ala Pro Pro Ile Ala Gly
420 425 430
Ser Ile Asn Cys Ser Ser Asp Ile Thr Gly Ile Ile Leu Thr Arg Asp
435 440 445
Gly Gly Asn Asn Asn Thr Asn Asn Glu Thr Phe Arg Pro Gly Gly Gly
450 455 460
Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val
465 470 475 480
Lys Ile Glu Pro Val Gly Val Ala Pro Thr Arg Ala Arg Arg Arg Val
485 490 495
Val Gln Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Val Phe Leu Gly
500 505 510
Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu
515 520 525
Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser
530 535 540
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Arg Leu Thr
545 550 555 560
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Leu Glu Ser
565 570 575
Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
580 585 590
Leu Ile Cys Thr Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Lys
595 600 605
Ser Tyr Asn Asp Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys
610 615 620
Glu Ile Asn Asn Tyr Thr Gln Ile Ile Tyr Glu Leu Leu Glu Glu Ser
625 630 635 640
Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys
645 650 655
Trp Ala Asn Leu Trp Asn Trp Phe Asn Ile Ser Asn Trp Leu Trp Tyr
660 665 670
Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile
675 680 685
Ile Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser
690 695 700
Pro Leu Ser Leu Gln Thr Leu Ile Pro Thr Thr Gln Arg Gly Pro Asp
705 710 715 720
Arg Pro Glu Gly Thr Glu Glu Glu Gly Gly Glu Gln Asp Arg Ser Arg
725 730 735
Ser Ile Arg Leu Val Asn Gly Phe Leu Pro Leu Ile Trp Asp Asp Leu
740 745 750
Arg Asn Leu Cys Leu Phe Ser Tyr Arg His Leu Arg Asn Leu Leu Leu
755 760 765
Ile Val Ala Arg Thr Val Glu Leu Leu Gly Ile Arg Gly Trp Glu Ala
770 775 780
Leu Lys Tyr Leu Trp Asn Leu Leu Leu Tyr Trp Gly Gln Glu Leu Arg
785 790 795 800
Asn Ser Ala Ile Asn Leu Leu Asp Thr Thr Ala Ile Ala Val Ala Glu
805 810 815
Gly Thr Asp Arg Ile Ile Glu Ala Val Gln Arg Ala Cys Arg Ala Ile
820 825 830
Arg Asn Ile Pro Arg Arg Ile Arg Gln Gly Leu Glu Arg Ala Leu Leu
835 840 845
<210> 57
<211> 832
<212> PRT
<213> 人类免疫缺陷病毒
<400> 57
Met Arg Val Lys Gly Ile Gln Lys Asn Trp Gln His Leu Trp Lys Trp
1 5 10 15
Gly Thr Leu Ile Leu Gly Leu Val Ile Ile Cys Ser Ala Ser Asn Asn
20 25 30
Met Trp Val Thr Val Tyr Tyr Gly Val Pro Ala Trp Glu Asp Ala Asp
35 40 45
Thr Ile Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Ser Ala Glu Lys
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Ala Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn His Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Glu Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asn Val Thr Lys Asn Asn Asn Thr Lys Ile Met Gly Arg
130 135 140
Glu Glu Ile Lys Asn Cys Ser Phe Asn Val Thr Thr Glu Ile Arg Asp
145 150 155 160
Lys Lys Lys Lys Glu Tyr Ala Leu Phe Tyr Arg Leu Asp Val Val Pro
165 170 175
Ile Asp Asp Asn Asn Asn Ser Tyr Arg Leu Ile Asn Cys Asn Ala Ser
180 185 190
Thr Ile Lys Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile
195 200 205
His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Arg Asp Lys
210 215 220
Asn Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys
225 230 235 240
Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly
245 250 255
Ser Leu Ala Glu Glu Glu Ile Ile Ile Lys Ser Glu Asn Leu Thr Asp
260 265 270
Asn Thr Lys Thr Ile Ile Val Gln Leu Asn Lys Ser Val Glu Ile Arg
275 280 285
Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Ser Phe Gly Pro
290 295 300
Gly Gln Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln
305 310 315 320
Ala His Cys Asn Val Ser Arg Thr Asp Trp Asn Asn Met Leu Gln Asn
325 330 335
Val Thr Ala Lys Leu Lys Glu Leu Phe Asn Lys Asn Ile Thr Phe Asn
340 345 350
Ser Ser Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys
355 360 365
Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gln Leu Phe Asn Ser Thr
370 375 380
Arg Pro Asn Glu Thr Asn Thr Ile Thr Leu Pro Cys Lys Ile Lys Gln
385 390 395 400
Ile Val Arg Met Trp Gln Arg Val Gly Gln Ala Met Tyr Ala Pro Pro
405 410 415
Ile Ala Gly Asn Ile Thr Cys Thr Ser Asn Ile Thr Gly Leu Leu Leu
420 425 430
Thr Arg Asp Gly Asn Asn Asn Asp Ser Glu Thr Phe Arg Pro Gly Gly
435 440 445
Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val
450 455 460
Val Lys Ile Lys Pro Leu Gly Ile Ala Pro Thr Arg Ala Arg Arg Arg
465 470 475 480
Val Val Gly Arg Glu Lys Arg Ala Val Gly Leu Gly Ala Val Phe Leu
485 490 495
Gly Phe Leu Gly Thr Ala Gly Ser Thr Met Gly Ala Ala Ser Ile Thr
500 505 510
Leu Thr Val Gln Val Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln
515 520 525
Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu
530 535 540
Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu
545 550 555 560
Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly
565 570 575
Lys Leu Ile Cys Pro Thr Asn Val Pro Trp Asn Ala Ser Trp Ser Asn
580 585 590
Lys Thr Tyr Asn Glu Ile Trp Asp Asn Met Thr Trp Ile Glu Trp Asp
595 600 605
Arg Glu Ile Asn Asn Tyr Thr Gln Gln Ile Tyr Ser Leu Ile Glu Glu
610 615 620
Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp
625 630 635 640
Lys Trp Ala Ser Leu Trp Ser Trp Phe Asp Ile Ser Asn Trp Leu Trp
645 650 655
Tyr Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg
660 665 670
Ile Val Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr
675 680 685
Ser Pro Leu Ser Leu Gln Thr Leu Ile Pro Asn Pro Thr Gly Ala Asp
690 695 700
Arg Pro Gly Glu Ile Glu Glu Gly Gly Gly Glu Gln Gly Arg Thr Arg
705 710 715 720
Ser Ile Arg Leu Val Asn Gly Phe Leu Ala Leu Ala Trp Asp Asp Leu
725 730 735
Arg Ser Leu Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Phe Val Leu
740 745 750
Ile Ala Ala Arg Thr Val Glu Thr Leu Gly His Arg Gly Trp Glu Ile
755 760 765
Leu Lys Tyr Leu Gly Asn Leu Val Cys Tyr Trp Gly Gln Glu Leu Lys
770 775 780
Asn Ser Ala Ile Ser Leu Leu Asp Thr Thr Ala Ile Ala Val Ala Asn
785 790 795 800
Trp Thr Asp Arg Val Ile Glu Val Val Gln Arg Val Phe Arg Ala Phe
805 810 815
Leu Asn Ile Pro Arg Arg Ile Arg Gln Gly Phe Glu Arg Ala Leu Leu
820 825 830
<210> 58
<211> 858
<212> PRT
<213> 人类免疫缺陷病毒
<400> 58
Met Arg Val Arg Gly Thr Arg Arg Asn Tyr Gln Gln Trp Trp Ile Trp
1 5 10 15
Gly Val Leu Gly Phe Trp Met Leu Met Ile Cys Asn Val Glu Gly Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Lys
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Glu Thr Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Val Met Glu Asn Val Thr Glu Asn Phe Asn Met Trp Asn
85 90 95
Asn Asp Met Val Asn Gln Met His Glu Asp Val Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Glu Cys Thr Asn Val Ser Ser Asn Gly Asn Gly Thr Tyr Asn Glu Thr
130 135 140
Tyr Asn Glu Ser Val Lys Glu Ile Lys Asn Cys Ser Phe Asn Ala Thr
145 150 155 160
Thr Leu Leu Arg Asp Arg Lys Lys Thr Val Tyr Ala Leu Phe Tyr Arg
165 170 175
Leu Asp Ile Val Pro Leu Asn Asp Glu Asn Ser Gly Lys Asn Ser Ser
180 185 190
Glu Tyr Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala
195 200 205
Cys Pro Lys Val Thr Phe Asp Pro Ile Pro Ile His Tyr Cys Thr Pro
210 215 220
Ala Gly Tyr Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe Asn Gly Thr
225 230 235 240
Gly Gln Cys His Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys
245 250 255
Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Arg
260 265 270
Glu Ile Ile Ile Arg Ser Glu Asn Leu Thr Asn Asn Val Lys Thr Ile
275 280 285
Ile Val His Leu Asn Gln Ser Val Glu Ile Val Cys Thr Arg Pro Asn
290 295 300
Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly Pro Gly Gln Thr Phe Tyr
305 310 315 320
Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile
325 330 335
Ser Lys Asp Lys Trp Tyr Glu Thr Leu Gln Arg Val Ser Lys Lys Leu
340 345 350
Ala Glu His Phe Pro Asn Lys Thr Ile Lys Phe Ala Ser Ser Ser Gly
355 360 365
Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys Arg Gly Glu Phe
370 375 380
Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn Gly Thr Tyr Met Asn Gly
385 390 395 400
Thr Asn Asn Ser Ser Ser Ile Ile Thr Ile Pro Cys Arg Ile Lys Gln
405 410 415
Ile Ile Asn Met Trp Gln Glu Val Gly Arg Ala Met Tyr Ala Pro Pro
420 425 430
Ile Glu Gly Asn Ile Thr Cys Lys Ser Asn Ile Thr Gly Leu Leu Leu
435 440 445
Val Arg Asp Gly Gly Arg Thr Glu Ser Asn Asn Thr Glu Ile Phe Arg
450 455 460
Pro Gly Gly Gly Asp Met Arg Asn Asn Trp Arg Asn Glu Leu Tyr Lys
465 470 475 480
Tyr Lys Val Val Glu Ile Lys Pro Leu Gly Val Ala Pro Thr Ala Ala
485 490 495
Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val Gly Leu Gly Ala
500 505 510
Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala
515 520 525
Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val
530 535 540
Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Met
545 550 555 560
Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Thr Arg Val Leu
565 570 575
Ala Ile Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly
580 585 590
Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ser Ser
595 600 605
Trp Ser Asn Lys Ser Gln Gln Glu Ile Trp Asp Asn Met Thr Trp Met
610 615 620
Gln Trp Asp Lys Glu Ile Ser Asn Tyr Thr Asn Thr Ile Tyr Arg Leu
625 630 635 640
Leu Glu Asp Ser Gln Asn Gln Gln Glu Arg Asn Glu Lys Asp Leu Leu
645 650 655
Ala Leu Asp Ser Trp Lys Asn Leu Trp Ser Trp Phe Asp Ile Thr Asn
660 665 670
Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Ile
675 680 685
Gly Leu Arg Ile Ile Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg
690 695 700
Gln Gly Tyr Ser Pro Leu Ser Phe Gln Ile Leu Thr Pro Asn Pro Gly
705 710 715 720
Gly Pro Gly Arg Leu Gly Arg Ile Glu Glu Glu Gly Gly Glu Gln Asp
725 730 735
Lys Thr Arg Ser Ile Arg Leu Val Asn Gly Phe Leu Ala Leu Ala Trp
740 745 750
Asp Asp Leu Arg Asn Leu Cys Leu Phe Ser Tyr His Arg Leu Arg Asp
755 760 765
Phe Ile Leu Leu Thr Ala Arg Gly Val Glu Leu Leu Gly Arg Asn Ser
770 775 780
Leu Arg Gly Leu Gln Arg Gly Trp Glu Ala Leu Lys Tyr Leu Gly Ser
785 790 795 800
Leu Val Gln Tyr Trp Gly Leu Glu Leu Lys Lys Ser Thr Ile Ser Leu
805 810 815
Val Asp Thr Ile Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Ile Ile
820 825 830
Asn Ile Val Gln Gly Ile Cys Arg Ala Ile His Asn Ile Pro Arg Arg
835 840 845
Ile Arg Gln Gly Phe Glu Ala Ala Leu Gln
850 855
<210> 59
<211> 837
<212> PRT
<213> 人类免疫缺陷病毒
<400> 59
Met Arg Val Met Gly Ile Gln Arg Asn Cys Gln Gln Trp Trp Ile Trp
1 5 10 15
Gly Ile Leu Gly Phe Trp Met Leu Met Ile Cys Asn Ala Thr Gly Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Thr Thr
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Lys Ala Glu Ala
50 55 60
His Asn Ile Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Val Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Gly Met Val Asp Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Gly Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Ser Asp Val Asn Ala Thr Asn Ser Ala Thr Asn Thr Val Val
130 135 140
Ala Gly Met Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Arg Asp
145 150 155 160
Lys Lys Lys Gln Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Gln
165 170 175
Ile Asp Gly Ser Asn Thr Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser
180 185 190
Ala Ile Thr Gln Ala Cys Pro Lys Val Thr Phe Glu Pro Ile Pro Ile
195 200 205
His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys
210 215 220
Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys
225 230 235 240
Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly
245 250 255
Ser Leu Ala Glu Glu Glu Ile Ile Ile Arg Ser Glu Asn Leu Thr Asp
260 265 270
Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Glu Ser Val Thr Ile Asn
275 280 285
Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly Pro
290 295 300
Gly Gln Thr Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asn Ile Arg Gln
305 310 315 320
Ala Tyr Cys Asn Ile Ser Gly Thr Glu Trp Asn Lys Thr Leu Gln Gln
325 330 335
Val Ala Lys Lys Leu Gly Asp Leu Leu Asn Lys Thr Thr Ile Ile Phe
340 345 350
Lys Pro Ser Ser Gly Gly Asp Pro Glu Ile Thr Thr His Thr Phe Asn
355 360 365
Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Lys Leu Phe Asn Ser
370 375 380
Ser Trp Thr Ser Asn Asn Thr Gly Asn Thr Ser Thr Ile Thr Leu Pro
385 390 395 400
Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Gly Val Gly Lys Ala
405 410 415
Ile Tyr Ala Pro Pro Ile Ala Gly Leu Ile Asn Cys Ser Ser Asn Ile
420 425 430
Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Ala Asn Asn Ser Glu Thr
435 440 445
Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu
450 455 460
Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Leu Ala Pro Thr
465 470 475 480
Lys Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Ile Gly Leu
485 490 495
Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly
500 505 510
Ala Ala Ser Leu Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly
515 520 525
Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln
530 535 540
His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg
545 550 555 560
Val Leu Ala Val Glu Ser Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile
565 570 575
Trp Gly Cys Ser Gly Lys His Ile Cys Thr Thr Asn Val Pro Trp Asn
580 585 590
Ser Ser Trp Ser Asn Lys Ser Leu Glu Glu Ile Trp Asp Asn Met Thr
595 600 605
Trp Met Glu Trp Glu Arg Glu Ile Asp Asn Tyr Thr Gly Leu Ile Tyr
610 615 620
Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu
625 630 635 640
Leu Leu Gln Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Ser Ile
645 650 655
Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val Gly Gly
660 665 670
Leu Ile Gly Leu Arg Ile Val Phe Ala Val Leu Ser Leu Val Asn Arg
675 680 685
Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu Leu Pro Ala
690 695 700
Pro Arg Gly Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu Gly Gly Glu
705 710 715 720
Gln Gly Arg Gly Arg Ser Ile Arg Leu Val Asn Gly Phe Ser Ala Leu
725 730 735
Ile Trp Asp Asp Leu Arg Asn Leu Cys Leu Phe Ser Tyr His Arg Leu
740 745 750
Arg Asp Leu Ile Leu Ile Ala Thr Arg Ile Val Glu Leu Leu Gly Arg
755 760 765
Arg Gly Trp Glu Ala Ile Lys Tyr Leu Trp Asn Leu Leu Gln Tyr Trp
770 775 780
Ile Gln Glu Leu Lys Asn Ser Ala Ile Ser Leu Leu Asp Thr Thr Ala
785 790 795 800
Ile Ala Val Ala Glu Gly Thr Asp Arg Ala Ile Glu Ile Val Gln Arg
805 810 815
Ala Val Arg Ala Val Leu Asn Ile Pro Thr Arg Ile Arg Gln Gly Leu
820 825 830
Glu Arg Ala Leu Leu
835
<210> 60
<211> 839
<212> PRT
<213> 人类免疫缺陷病毒
<400> 60
Met Arg Val Lys Glu Thr Gln Arg Asn Trp His Asn Leu Trp Arg Trp
1 5 10 15
Gly Leu Met Ile Phe Gly Met Leu Met Ile Cys Asn Ala Thr Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Asp Ala Asp
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Ile Pro Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Glu Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Val Lys Asn Ala Thr Asn Thr Thr Val Glu Ala Ala
130 135 140
Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Glu Ile Lys Asp Lys
145 150 155 160
Lys Lys Lys Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Pro Ile
165 170 175
Asn Asp Asn Asn Asn Ser Ile Tyr Arg Leu Ile Asn Cys Asn Val Ser
180 185 190
Thr Val Lys Gln Ala Cys Pro Lys Val Thr Phe Glu Pro Ile Pro Ile
195 200 205
His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys
210 215 220
Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys
225 230 235 240
Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly
245 250 255
Ser Leu Ala Glu Gly Glu Val Arg Ile Arg Ser Glu Asn Phe Thr Asn
260 265 270
Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Ser Ser Val Arg Ile Asn
275 280 285
Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His Ile Gly Pro
290 295 300
Gly Gln Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln
305 310 315 320
Ala His Cys Asn Ile Ser Arg Ala Glu Trp Asn Asn Thr Leu Gln Gln
325 330 335
Val Ala Lys Gln Leu Arg Glu Asn Phe Asn Lys Thr Ile Ile Phe Asn
340 345 350
Asn Pro Ser Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys
355 360 365
Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Arg Leu Phe Asn Ser Thr
370 375 380
Trp Asn Asn Asp Thr Arg Asn Asp Thr Lys Gln Met His Ile Thr Leu
385 390 395 400
Pro Cys Arg Ile Lys Gln Ile Val Asn Met Trp Gln Arg Val Gly Gln
405 410 415
Ala Met Tyr Ala Pro Pro Ile Gln Gly Lys Ile Arg Cys Asn Ser Asn
420 425 430
Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Asn Thr Asn
435 440 445
Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp Asn Trp Arg Ser
450 455 460
Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile Lys Pro Leu Gly Val Ala
465 470 475 480
Pro Thr Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val
485 490 495
Gly Ile Gly Ala Val Leu Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr
500 505 510
Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu
515 520 525
Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Lys Ala Ile Glu Ala
530 535 540
Gln Gln His Leu Leu Lys Leu Thr Val Trp Gly Ile Lys Gln Leu Gln
545 550 555 560
Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu
565 570 575
Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro
580 585 590
Trp Asn Phe Ser Trp Ser Asn Lys Ser Tyr Asp Glu Ile Trp Asp Asn
595 600 605
Met Thr Trp Ile Glu Trp Glu Arg Glu Ile Asn Asn Tyr Thr Gln Thr
610 615 620
Ile Tyr Thr Leu Leu Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu
625 630 635 640
Gln Asp Leu Leu Ala Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe
645 650 655
Asp Ile Ser Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val
660 665 670
Gly Gly Leu Ile Gly Leu Arg Ile Ile Phe Ala Val Leu Ser Ile Val
675 680 685
Asn Arg Cys Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr Leu Thr
690 695 700
Pro Asn His Lys Glu Ala Asp Arg Pro Gly Gly Ile Glu Glu Gly Gly
705 710 715 720
Gly Glu Gln Asp Arg Thr Arg Ser Ile Arg Leu Val Ser Gly Phe Leu
725 730 735
Ala Leu Ala Trp Asp Asp Leu Arg Asn Leu Cys Leu Phe Ser Tyr His
740 745 750
Arg Leu Arg Asp Phe Ile Leu Ile Ala Ala Arg Ile Val Glu Thr Leu
755 760 765
Gly Arg Arg Gly Trp Glu Ile Leu Lys Tyr Leu Gly Asn Leu Ala Gln
770 775 780
Tyr Trp Gly Gln Glu Leu Lys Asn Ser Ala Ile Ser Leu Leu Asn Ala
785 790 795 800
Thr Ala Ile Ala Val Ala Glu Gly Thr Asp Arg Ile Ile Glu Val Val
805 810 815
His Arg Val Leu Arg Ala Ile Leu His Ile Pro Arg Arg Ile Arg Gln
820 825 830
Gly Phe Glu Arg Ala Leu Leu
835
<210> 61
<211> 838
<212> PRT
<213> 人类免疫缺陷病毒
<400> 61
Met Arg Val Arg Gly Met Gln Arg Asn Trp Gln His Leu Gly Lys Trp
1 5 10 15
Gly Leu Leu Phe Leu Gly Ile Leu Ile Ile Cys Asn Ala Thr Glu Asn
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ser Tyr Glu Arg Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Val Asp Leu Glu Asn Val Thr Glu Asn Phe Asp Met Trp Lys
85 90 95
Asn Asn Met Val Glu Gln Met His Thr Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Ala Asn Ala Thr Ala Asn Ala Thr Lys Glu His Pro
130 135 140
Glu Gly Arg Ala Gly Ala Ile Gln Asn Cys Ser Phe Asn Met Thr Thr
145 150 155 160
Glu Val Arg Asp Lys Gln Met Lys Val Gln Ala Leu Phe Tyr Arg Leu
165 170 175
Asp Ile Val Pro Ile Ser Asp Asn Asn Ser Asn Glu Tyr Arg Leu Ile
180 185 190
Asn Cys Asn Thr Ser Thr Ile Thr Gln Ala Cys Pro Lys Val Ser Trp
195 200 205
Asp Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Tyr Ala Ile Leu
210 215 220
Lys Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val
225 230 235 240
Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln
245 250 255
Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Ile Ile Arg Ser
260 265 270
Gln Asn Ile Ser Asp Asn Ala Lys Thr Ile Ile Val His Leu Asn Glu
275 280 285
Ser Val Gln Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser
290 295 300
Ile His Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Asp Ile Ile
305 310 315 320
Gly Asp Ile Arg Lys Ala His Cys Asn Val Ser Gly Thr Gln Trp Asn
325 330 335
Lys Thr Leu Glu Gln Val Lys Lys Lys Leu Arg Ser Tyr Phe Asn Thr
340 345 350
Thr Ile Lys Phe Asn Ser Ser Ser Gly Gly Asp Pro Glu Ile Thr Met
355 360 365
His Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Lys
370 375 380
Leu Phe Asn Asp Thr Val Ser Asn Asp Thr Ile Ile Leu Pro Cys Arg
385 390 395 400
Ile Lys Gln Ile Val Asn Met Trp Gln Glu Val Gly Arg Ala Met Tyr
405 410 415
Ala Ala Pro Ile Ala Gly Asn Ile Thr Cys Thr Ser Asn Ile Thr Gly
420 425 430
Leu Leu Leu Thr Arg Asp Gly Gly His Asn Glu Thr Asn Lys Thr Glu
435 440 445
Thr Phe Arg Pro Gly Gly Gly Asn Met Lys Asp Asn Trp Arg Ser Glu
450 455 460
Leu Tyr Lys Tyr Lys Val Val Glu Ile Glu Pro Leu Gly Val Ala Pro
465 470 475 480
Thr Arg Ala Lys Arg Gln Val Val Lys Arg Glu Lys Arg Ala Val Gly
485 490 495
Ile Gly Ala Leu Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met
500 505 510
Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser
515 520 525
Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln
530 535 540
Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala
545 550 555 560
Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly
565 570 575
Leu Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro Trp
580 585 590
Asn Ser Ser Trp Ser Asn Lys Ser Gln Glu Glu Ile Trp Glu Asn Met
595 600 605
Thr Trp Met Glu Trp Glu Lys Glu Ile Asn Asn Tyr Ser Asn Glu Ile
610 615 620
Tyr Arg Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln
625 630 635 640
Glu Leu Leu Ala Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asp
645 650 655
Ile Ser Asn Trp Leu Trp Tyr Ile Arg Ile Phe Ile Met Ile Val Gly
660 665 670
Gly Leu Ile Gly Leu Arg Ile Val Phe Ala Val Leu Ser Ile Val Asn
675 680 685
Arg Val Arg Lys Gly Tyr Ser Pro Leu Ser Leu Gln Thr His Ile Pro
690 695 700
Ser Pro Arg Glu Pro Asp Arg Pro Glu Gly Ile Glu Glu Gly Gly Gly
705 710 715 720
Glu Gln Gly Lys Asp Arg Ser Val Arg Leu Val Asn Gly Phe Leu Ala
725 730 735
Leu Ile Trp Asp Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg
740 745 750
Leu Arg Asp Leu Leu Leu Ile Val Thr Arg Ile Val Glu Leu Leu Gly
755 760 765
Arg Arg Gly Trp Glu Val Leu Lys Tyr Trp Trp Asn Leu Leu Gln Tyr
770 775 780
Trp Ser Gln Glu Leu Lys Asn Ser Ala Ile Ser Leu Leu Asn Thr Thr
785 790 795 800
Ala Ile Val Val Ala Glu Gly Thr Asp Arg Val Ile Glu Ala Leu Gln
805 810 815
Arg Val Gly Arg Ala Ile Leu Asn Ile Pro Arg Arg Ile Arg Gln Gly
820 825 830
Leu Glu Arg Ala Leu Leu
835
<210> 62
<211> 855
<212> PRT
<213> 人类免疫缺陷病毒
<400> 62
Met Lys Ala Lys Gly Thr Gln Arg Asn Trp Gln Ser Leu Trp Lys Trp
1 5 10 15
Gly Thr Leu Ile Leu Gly Leu Val Ile Ile Cys Ser Ala Ser Asn Asp
20 25 30
Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala Thr
35 40 45
Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Ala Glu Val
50 55 60
His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro
65 70 75 80
Gln Glu Val Ala Leu Glu Asn Val Thr Glu Asn Phe Asn Met Trp Glu
85 90 95
Asn Asn Met Val Asp Gln Met Gln Glu Asp Ile Ile Ser Leu Trp Asp
100 105 110
Gln Ser Leu Lys Pro Cys Val Glu Leu Thr Pro Leu Cys Val Thr Leu
115 120 125
Asn Cys Thr Asp Phe Asn Asn Thr Thr Asn Asn Thr Thr Asn Thr Arg
130 135 140
Asn Asp Gly Glu Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr
145 150 155 160
Ser Leu Arg Asp Lys Ile Lys Lys Glu Tyr Ala Leu Phe Tyr Asn Leu
165 170 175
Asp Val Val Gln Met Asp Asn Asp Asn Ser Ser Tyr Arg Leu Thr Ser
180 185 190
Cys Asn Thr Ser Ile Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Thr
195 200 205
Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Val Ile Leu Lys
210 215 220
Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser
225 230 235 240
Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu
245 250 255
Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Val Ile Arg Ser Lys
260 265 270
Asn Phe Thr Asp Asn Ala Lys Thr Ile Ile Val Gln Leu Lys Asp Pro
275 280 285
Ile Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Arg Ile
290 295 300
Thr Met Gly Pro Gly Arg Val Leu Tyr Thr Thr Gly Gln Ile Ile Gly
305 310 315 320
Asp Ile Arg Lys Ala His Cys Asn Ile Ser Lys Thr Lys Trp Asn Asn
325 330 335
Thr Leu Gly Gln Ile Val Lys Lys Leu Arg Glu Gln Phe Met Asn Lys
340 345 350
Thr Ile Val Phe Gln Arg Ser Ser Gly Gly Asp Pro Glu Ile Val Met
355 360 365
His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln
370 375 380
Leu Phe Asn Ser Thr Trp Arg Ser Asn Ser Thr Trp Asn Asp Thr Thr
385 390 395 400
Glu Thr Asn Asn Thr Asp Leu Ile Thr Leu Pro Cys Arg Ile Lys Gln
405 410 415
Ile Val Asn Met Trp Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro
420 425 430
Ile Ser Gly Gln Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu
435 440 445
Ile Arg Asp Gly Gly Ser Asn Asn Thr Glu Thr Phe Arg Pro Gly Gly
450 455 460
Gly Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val
465 470 475 480
Val Lys Ile Glu Pro Leu Gly Val Ala Pro Thr Arg Ala Lys Arg Arg
485 490 495
Val Val Gln Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Leu Leu Phe
500 505 510
Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr
515 520 525
Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln
530 535 540
Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Met Leu Gln Leu
545 550 555 560
Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu
565 570 575
Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly
580 585 590
Lys Leu Ile Cys Thr Thr Thr Val Pro Trp Asn Ala Ser Trp Ser Asn
595 600 605
Lys Ser Leu Asp Asp Ile Trp Asn Asn Met Thr Trp Met Glu Trp Glu
610 615 620
Arg Glu Ile Asp Asn Tyr Thr Gly Leu Ile Tyr Thr Leu Ile Glu Gln
625 630 635 640
Ser Gln Asn Gln Gln Glu Arg Asn Glu Gln Glu Leu Leu Glu Leu Asp
645 650 655
Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp
660 665 670
Tyr Ile Lys Ile Phe Ile Met Ile Ile Gly Gly Leu Ile Gly Leu Arg
675 680 685
Ile Val Phe Ala Val Leu Ser Ile Ile Asn Arg Val Arg Lys Gly Tyr
690 695 700
Ser Pro Leu Ser Phe Gln Thr Leu Thr His His Gln Arg Glu Pro Asp
705 710 715 720
Arg Pro Gly Arg Ile Glu Glu Glu Gly Gly Glu Gln Asp Lys Asp Arg
725 730 735
Ser Ile Arg Leu Val Ser Gly Phe Leu Ala Leu Ala Trp Asp Asp Leu
740 745 750
Arg Ser Leu Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Phe Ile Leu
755 760 765
Ile Ala Ala Arg Thr Val Glu Leu Leu Gly Arg Ser Ser Leu Lys Gly
770 775 780
Leu Arg Leu Gly Trp Glu Gly Leu Lys Tyr Leu Trp Asn Leu Leu Leu
785 790 795 800
Tyr Trp Gly Arg Glu Leu Lys Asn Ser Ala Ile Asn Leu Leu Asp Thr
805 810 815
Val Ala Ile Ala Val Ala Asn Trp Thr Asp Arg Ala Ile Glu Val Val
820 825 830
Gln Arg Val Gly Arg Ala Val Leu Asn Ile Pro Val Arg Ile Arg Gln
835 840 845
Gly Leu Glu Arg Ala Leu Leu
850 855
<210> 63
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 63
Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Val Phe
1 5 10 15
Ala Val Leu Ser Ile Val
20
<210> 64
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 64
Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Val Phe
1 5 10 15
Ala Val Leu Ser Val Ile
20
<210> 65
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 65
Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Val Ile
1 5 10 15
Ala Ile Ile Ser Val Val
20
<210> 66
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 66
Ile Phe Ile Met Ile Val Gly Gly Leu Val Gly Leu Arg Ile Val Phe
1 5 10 15
Ala Val Leu Ser Ile Val
20
<210> 67
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 67
Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Ile Phe
1 5 10 15
Ala Val Leu Ser Ile Val
20
<210> 68
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 68
Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Val Phe
1 5 10 15
Ala Val Leu Ser Leu Val
20
<210> 69
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 69
Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Val Phe
1 5 10 15
Ala Val Leu Ser Val Val
20
<210> 70
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 70
Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Val Phe
1 5 10 15
Ala Val Leu Thr Ile Ile
20
<210> 71
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒2型
<400> 71
Ile Phe Ile Met Ile Val Gly Gly Leu Val Gly Leu Arg Ile Ile Phe
1 5 10 15
Ala Val Leu Ser Ile Val
20
<210> 72
<211> 22
<212> PRT
<213> 人类免疫缺陷病毒
<400> 72
Ile Phe Ile Met Ile Ile Gly Gly Leu Ile Gly Leu Arg Ile Val Phe
1 5 10 15
Ala Val Leu Ser Ile Ile
20
<210> 73
<211> 12
<212> PRT
<213> 合成的
<400> 73
Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala
1 5 10
<210> 74
<211> 20
<212> PRT
<213> 合成的
<400> 74
Thr Trp Ile Gln Asn Pro Gly Thr Lys Trp Tyr Gln Asn Pro Gly Thr
1 5 10 15
Lys Ile Tyr Thr
20
<210> 75
<211> 8
<212> PRT
<213> 合成的
<400> 75
Ser Gly Ser Gly Ala Ser Gly Ser
1 5
<210> 76
<211> 4
<212> PRT
<213> 合成的
<400> 76
Pro Ser Gly Pro
1
<210> 77
<211> 216
<212> PRT
<213> 合成的
<400> 77
Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys
1 5 10 15
Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val
20 25 30
Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe
35 40 45
Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu
50 55 60
Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His
65 70 75 80
Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys
85 90 95
Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser
100 105 110
Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met
115 120 125
Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro
130 135 140
Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn
145 150 155 160
Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met
165 170 175
Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser
180 185 190
Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr
195 200 205
Lys Ser Phe Ser Arg Thr Pro Gly
210 215
<210> 78
<211> 231
<212> PRT
<213> 合成的
<400> 78
Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala
1 5 10 15
Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile
20 25 30
Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val
35 40 45
Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val
50 55 60
Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp
65 70 75 80
Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln
85 90 95
Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp
100 105 110
Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val
115 120 125
Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr
130 135 140
Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu
145 150 155 160
Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr
165 170 175
Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr
180 185 190
Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr
195 200 205
Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr Lys
210 215 220
Ser Phe Ser Arg Thr Pro Gly
225 230
<210> 79
<211> 15
<212> PRT
<213> 合成的
<400> 79
Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro
1 5 10 15
<210> 80
<211> 213
<212> PRT
<213> 合成的
<400> 80
Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
1 5 10 15
Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp
20 25 30
Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp
35 40 45
Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn
50 55 60
Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp
65 70 75 80
Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro
85 90 95
Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala
100 105 110
Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp
115 120 125
Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile
130 135 140
Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn
145 150 155 160
Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys
165 170 175
Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys
180 185 190
Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu
195 200 205
Ser His Ser Pro Gly
210
<210> 81
<211> 40
<212> PRT
<213> 合成的
<400> 81
Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu
1 5 10 15
Arg Phe Glu Met Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp
20 25 30
Ala Gln Ala Gly Lys Glu Pro Gly
35 40
<210> 82
<211> 27
<212> PRT
<213> 合成的
<400> 82
Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys
1 5 10 15
Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
20 25
<210> 83
<211> 94
<212> PRT
<213> 合成的
<400> 83
Gly Ser His Met Trp Lys Gln Ser Val Glu Leu Ala Lys Lys Asp Ser
1 5 10 15
Leu Tyr Lys Asp Ala Met Gln Tyr Ala Ser Glu Ser Lys Asp Thr Glu
20 25 30
Leu Ala Glu Glu Leu Leu Gln Trp Phe Leu Gln Glu Glu Lys Arg Glu
35 40 45
Cys Phe Gly Ala Cys Leu Phe Thr Cys Tyr Asp Leu Leu Arg Pro Asp
50 55 60
Val Val Leu Glu Leu Ala Trp Arg His Asn Ile Met Asp Phe Ala Met
65 70 75 80
Pro Tyr Phe Ile Gln Val Met Lys Glu Tyr Leu Thr Lys Val
85 90
<210> 84
<211> 20
<212> PRT
<213> 合成的
<400> 84
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser
20
<210> 85
<211> 6
<212> PRT
<213> 合成的
<400> 85
His His His His His His
1 5
<210> 86
<211> 905
<212> PRT
<213> 合成的
<400> 86
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Gly Val Pro Val Trp Lys Asp Ala Glu Thr Thr Leu
20 25 30
Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val His Asn Val
35 40 45
Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro Gln Glu Ile
50 55 60
His Leu Glu Asn Val Thr Glu Asp Phe Asn Met Trp Lys Asn Asn Met
65 70 75 80
Val Glu Gln Met His Thr Asp Ile Ile Ser Leu Trp Asp Gln Ser Leu
85 90 95
Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu Asp Cys Asn
100 105 110
Ala Thr Ala Ser Asn Val Thr Asn Glu Met Arg Asn Cys Ser Phe Asn
115 120 125
Ile Thr Thr Glu Leu Lys Asp Lys Lys Gln Gln Val Tyr Ser Leu Phe
130 135 140
Tyr Lys Leu Asp Val Val Gln Ile Asn Glu Lys Asn Glu Thr Asp Lys
145 150 155 160
Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala Cys Pro
165 170 175
Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly
180 185 190
Phe Ala Ile Leu Lys Cys Lys Asp Thr Glu Phe Asn Gly Thr Gly Pro
195 200 205
Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val
210 215 220
Ile Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Gly Ile
225 230 235 240
Gln Ile Arg Ser Glu Asn Ile Thr Asn Asn Ala Lys Thr Ile Ile Val
245 250 255
Gln Leu Asp Lys Ala Val Lys Ile Asn Cys Thr Arg Pro Asn Asn Asn
260 265 270
Thr Arg Lys Gly Val Arg Ile Gly Pro Gly Gln Ala Phe Tyr Ala Thr
275 280 285
Gly Gly Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Val Ser Arg
290 295 300
Ala Lys Trp Asn Asp Thr Leu Arg Gly Val Ala Lys Lys Leu Arg Glu
305 310 315 320
His Phe Lys Asn Lys Thr Ile Ile Phe Glu Lys Ser Ser Gly Gly Asp
325 330 335
Ile Glu Ile Thr Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr
340 345 350
Cys Asn Thr Ser Gly Leu Phe Asn Ser Thr Trp Glu Ser Asn Ser Thr
355 360 365
Glu Ser Asn Asn Thr Thr Ser Asn Asp Thr Ile Thr Leu Thr Cys Arg
370 375 380
Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly Gln Ala Met Tyr
385 390 395 400
Ala Pro Pro Ile Gln Gly Val Ile Arg Cys Glu Ser Asn Ile Thr Gly
405 410 415
Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Ser Thr Asn Glu Ile Phe
420 425 430
Arg Pro Gly Gly Gly Asn Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr
435 440 445
Lys Tyr Lys Val Val Lys Ile Glu Pro Ser Gly Pro Val Pro Glu Val
450 455 460
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
465 470 475 480
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
485 490 495
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
500 505 510
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
515 520 525
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
530 535 540
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
545 550 555 560
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
565 570 575
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
580 585 590
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
595 600 605
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
610 615 620
Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln
625 630 635 640
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
645 650 655
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
660 665 670
Gly Ile Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val His Gln Ala
675 680 685
Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val Glu Glu Lys
690 695 700
Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu Ser Glu Gly
705 710 715 720
Ala Thr Pro Gln Asp Leu Asn Thr Met Leu Asn Thr Val Gly Gly His
725 730 735
Gln Ala Ala Met Gln Met Leu Lys Glu Thr Ile Asn Glu Glu Ala Ala
740 745 750
Glu Trp Asp Arg Val His Pro Val His Ala Gly Pro Ile Ala Pro Gly
755 760 765
Gln Met Arg Glu Pro Arg Gly Ser Asp Ile Ala Gly Thr Thr Ser Thr
770 775 780
Leu Gln Glu Gln Ile Gly Trp Met Thr Asn Asn Pro Pro Ile Pro Val
785 790 795 800
Gly Glu Ile Tyr Lys Arg Trp Ile Ile Leu Gly Leu Asn Lys Ile Val
805 810 815
Arg Met Tyr Ser Pro Thr Ser Ile Leu Asp Ile Arg Gln Gly Pro Lys
820 825 830
Glu Pro Phe Arg Asp Tyr Val Asp Arg Phe Tyr Lys Thr Leu Arg Ala
835 840 845
Glu Gln Ala Ser Gln Asp Val Lys Asn Trp Met Thr Glu Thr Leu Leu
850 855 860
Val Gln Asn Ala Asn Pro Asp Cys Lys Thr Ile Leu Lys Ala Leu Gly
865 870 875 880
Pro Ala Ala Thr Leu Glu Glu Met Met Thr Ala Cys Gln Gly Val Gly
885 890 895
Gly Pro Gly His Lys Ala Arg Val Leu
900 905
<210> 87
<211> 914
<212> PRT
<213> 合成的
<400> 87
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Gly Val Pro Val Trp Lys Asp Ala Glu Thr Thr Leu
20 25 30
Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu Val His Asn Val
35 40 45
Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn Pro Gln Glu Ile
50 55 60
His Leu Glu Asn Val Thr Glu Asp Phe Asn Met Trp Lys Asn Asn Met
65 70 75 80
Val Glu Gln Met His Thr Asp Ile Ile Ser Leu Trp Asp Gln Ser Leu
85 90 95
Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Thr Leu Asp Cys Asn
100 105 110
Ala Thr Ala Ser Asn Val Thr Asn Glu Met Arg Asn Cys Ser Phe Asn
115 120 125
Ile Thr Thr Glu Leu Lys Asp Lys Lys Gln Gln Val Tyr Ser Leu Phe
130 135 140
Tyr Lys Leu Asp Val Val Gln Ile Asn Glu Lys Asn Glu Thr Asp Lys
145 150 155 160
Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala Cys Pro
165 170 175
Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly
180 185 190
Phe Ala Ile Leu Lys Cys Lys Asp Thr Glu Phe Asn Gly Thr Gly Pro
195 200 205
Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val
210 215 220
Ile Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Gly Ile
225 230 235 240
Gln Ile Arg Ser Glu Asn Ile Thr Asn Asn Ala Lys Thr Ile Ile Val
245 250 255
Gln Leu Asp Lys Ala Val Lys Ile Asn Cys Thr Arg Pro Asn Asn Asn
260 265 270
Thr Arg Lys Gly Val Arg Ile Gly Pro Gly Gln Ala Phe Tyr Ala Thr
275 280 285
Gly Gly Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Val Ser Arg
290 295 300
Ala Lys Trp Asn Asp Thr Leu Arg Gly Val Ala Lys Lys Leu Arg Glu
305 310 315 320
His Phe Lys Asn Lys Thr Ile Ile Phe Glu Lys Ser Ser Gly Gly Asp
325 330 335
Ile Glu Ile Thr Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr
340 345 350
Cys Asn Thr Ser Gly Leu Phe Asn Ser Thr Trp Glu Ser Asn Ser Thr
355 360 365
Glu Ser Asn Asn Thr Thr Ser Asn Asp Thr Ile Thr Leu Thr Cys Arg
370 375 380
Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly Gln Ala Met Tyr
385 390 395 400
Ala Pro Pro Ile Gln Gly Val Ile Arg Cys Glu Ser Asn Ile Thr Gly
405 410 415
Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Ser Thr Asn Glu Ile Phe
420 425 430
Arg Pro Gly Gly Gly Asn Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr
435 440 445
Lys Tyr Lys Val Val Lys Ile Glu Val Pro Arg Asp Cys Gly Cys Lys
450 455 460
Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
465 470 475 480
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
485 490 495
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
500 505 510
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
515 520 525
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
530 535 540
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
545 550 555 560
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
565 570 575
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
580 585 590
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
595 600 605
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
610 615 620
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
625 630 635 640
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
645 650 655
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
660 665 670
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Ile Pro Ile Val Gln Asn
675 680 685
Leu Gln Gly Gln Met Val His Gln Ala Ile Ser Pro Arg Thr Leu Asn
690 695 700
Ala Trp Val Lys Val Val Glu Glu Lys Ala Phe Ser Pro Glu Val Ile
705 710 715 720
Pro Met Phe Ser Ala Leu Ser Glu Gly Ala Thr Pro Gln Asp Leu Asn
725 730 735
Thr Met Leu Asn Thr Val Gly Gly His Gln Ala Ala Met Gln Met Leu
740 745 750
Lys Glu Thr Ile Asn Glu Glu Ala Ala Glu Trp Asp Arg Val His Pro
755 760 765
Val His Ala Gly Pro Ile Ala Pro Gly Gln Met Arg Glu Pro Arg Gly
770 775 780
Ser Asp Ile Ala Gly Thr Thr Ser Thr Leu Gln Glu Gln Ile Gly Trp
785 790 795 800
Met Thr Asn Asn Pro Pro Ile Pro Val Gly Glu Ile Tyr Lys Arg Trp
805 810 815
Ile Ile Leu Gly Leu Asn Lys Ile Val Arg Met Tyr Ser Pro Thr Ser
820 825 830
Ile Leu Asp Ile Arg Gln Gly Pro Lys Glu Pro Phe Arg Asp Tyr Val
835 840 845
Asp Arg Phe Tyr Lys Thr Leu Arg Ala Glu Gln Ala Ser Gln Asp Val
850 855 860
Lys Asn Trp Met Thr Glu Thr Leu Leu Val Gln Asn Ala Asn Pro Asp
865 870 875 880
Cys Lys Thr Ile Leu Lys Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu
885 890 895
Met Met Thr Ala Cys Gln Gly Val Gly Gly Pro Gly His Lys Ala Arg
900 905 910
Val Leu
<210> 88
<211> 894
<212> PRT
<213> 合成的
<400> 88
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Gly Val Pro Val Trp Arg Asn Ala Ser Ile Pro Leu
20 25 30
Phe Cys Ala Thr Lys Asn Arg Asp Thr Trp Gly Thr Ile Gln Cys Leu
35 40 45
Pro Asp Asn Asp Asp Tyr Gln Glu Ile Ala Leu Asn Val Thr Glu Ala
50 55 60
Phe Asp Ala Trp Asn Asn Thr Val Thr Glu Gln Ala Val Glu Asp Val
65 70 75 80
Trp Ser Leu Phe Glu Thr Ser Ile Lys Pro Cys Val Lys Leu Thr Pro
85 90 95
Leu Cys Val Ala Met Ser Cys Asn Ser Thr Thr Ile Pro Pro Ser Glu
100 105 110
Glu Met Val Asp Cys Gln Phe Asn Met Thr Gly Leu Asp Arg Asp Lys
115 120 125
Lys Lys Gln Tyr Asn Glu Thr Trp Tyr Ser Lys Asp Val Val Cys Glu
130 135 140
Leu Asn Lys Thr Asp Gly Gly Arg Gly Arg Cys Tyr Met Asn His Cys
145 150 155 160
Asn Thr Ser Val Ile Thr Glu Ser Cys Asp Lys His Tyr Trp Asp Ala
165 170 175
Ile Arg Phe Arg Tyr Cys Ala Pro Pro Gly Phe Ala Leu Leu Arg Cys
180 185 190
Asn Asp Thr Asn Tyr Ser Gly Phe Met Pro Asn Cys Ser Lys Val Val
195 200 205
Val Ser Ser Cys Thr Arg Met Met Glu Thr Gln Thr Ser Thr Trp Leu
210 215 220
Gly Phe Asn Gly Thr Arg Ala Glu Asn Arg Thr Tyr Met Tyr Trp His
225 230 235 240
Ser Lys Asp Asn Arg Thr Ile Ile Ser Leu Asn Lys Tyr Tyr Asn Leu
245 250 255
Thr Met His Cys Lys Arg Pro Gly Asn Lys Thr Val Ala Pro Ile Thr
260 265 270
Leu Met Ser Gly Leu Val Phe His Ser Gln Pro Ile Asn Arg Arg Pro
275 280 285
Arg Gln Ala Trp Cys Trp Phe Lys Gly Gln Trp Arg Glu Ala Met Gln
290 295 300
Glu Val Lys Arg Thr Leu Ile Lys His Pro Arg Tyr Lys Gly Thr Asn
305 310 315 320
Asp Thr Arg Asn Ile Thr Phe Thr Lys Pro Gly Glu Gly Ser Asp Pro
325 330 335
Glu Val Ala Tyr Met Trp Thr Asn Cys Arg Gly Glu Phe Leu Tyr Cys
340 345 350
Asn Met Thr Trp Phe Leu Asn Trp Val Glu Asn Arg Thr Gly Gln Thr
355 360 365
Gln Arg Asn Tyr Ala Pro Cys His Ile Lys Gln Ile Ile Asn Thr Trp
370 375 380
His Lys Val Gly Lys Asn Val Tyr Leu Pro Pro Arg Glu Gly Glu Leu
385 390 395 400
Thr Cys Asn Ser Thr Val Thr Ser Ile Ile Ala Asn Ile Asp Val Asp
405 410 415
Ser Asn Asn Asn Arg Thr Asn Ile Thr Phe Ser Ala Glu Val Ala Glu
420 425 430
Leu Tyr Arg Leu Glu Leu Gly Asp Tyr Lys Leu Ile Glu Val Thr Pro
435 440 445
Ser Gly Pro Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys
450 455 460
Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val
465 470 475 480
Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe
485 490 495
Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu
500 505 510
Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His
515 520 525
Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala
530 535 540
Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg
545 550 555 560
Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met
565 570 575
Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro
580 585 590
Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn
595 600 605
Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val
610 615 620
Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr
625 630 635 640
Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu
645 650 655
Lys Ser Leu Ser His Ser Pro Gly Ile Val Gln Gln Ile Ala Gly Asn
660 665 670
Tyr Val His Met Pro Leu Ser Pro Arg Thr Leu Asn Ala Trp Val Lys
675 680 685
Leu Val Glu Glu Lys Lys Phe Gly Ala Glu Val Val Pro Gly Phe Gln
690 695 700
Ala Leu Ser Glu Gly Cys Thr Pro Tyr Asp Ile Asn Gln Met Leu Asn
705 710 715 720
Cys Val Gly Asp His Gln Ala Ala Met Gln Ile Ile Arg Glu Ile Ile
725 730 735
Asn Glu Glu Ala Ala Asp Trp Asp Gln Gln His Pro Ile Pro Gly Pro
740 745 750
Leu Pro Ala Gly Gln Leu Arg Asp Pro Arg Gly Ser Asp Ile Ala Gly
755 760 765
Thr Thr Ser Thr Val Glu Glu Gln Ile Gln Trp Met Tyr Arg Ala Gln
770 775 780
Asn Pro Val Pro Val Gly Asn Ile Tyr Arg Arg Trp Ile Gln Ile Gly
785 790 795 800
Leu Gln Lys Cys Val Arg Met Tyr Asn Pro Thr Asn Ile Leu Asp Ile
805 810 815
Lys Gln Gly Pro Lys Glu Pro Phe Gln Ser Tyr Val Asp Arg Phe Tyr
820 825 830
Lys Ser Leu Arg Ala Glu Gln Thr Asp Pro Ala Val Lys Asn Trp Met
835 840 845
Thr Gln Thr Leu Leu Ile Gln Asn Ala Asn Pro Asp Cys Lys Leu Val
850 855 860
Leu Lys Gly Leu Gly Met Asn Pro Thr Leu Glu Glu Met Leu Thr Ala
865 870 875 880
Cys Gln Gly Ile Gly Gly Pro Gly Gln Lys Ala Arg Leu Met
885 890
<210> 89
<211> 903
<212> PRT
<213> 合成的
<400> 89
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Gly Val Pro Val Trp Arg Asn Ala Ser Ile Pro Leu
20 25 30
Phe Cys Ala Thr Lys Asn Arg Asp Thr Trp Gly Thr Ile Gln Cys Leu
35 40 45
Pro Asp Asn Asp Asp Tyr Gln Glu Ile Ala Leu Asn Val Thr Glu Ala
50 55 60
Phe Asp Ala Trp Asn Asn Thr Val Thr Glu Gln Ala Val Glu Asp Val
65 70 75 80
Trp Ser Leu Phe Glu Thr Ser Ile Lys Pro Cys Val Lys Leu Thr Pro
85 90 95
Leu Cys Val Ala Met Ser Cys Asn Ser Thr Thr Ile Pro Pro Ser Glu
100 105 110
Glu Met Val Asp Cys Gln Phe Asn Met Thr Gly Leu Asp Arg Asp Lys
115 120 125
Lys Lys Gln Tyr Asn Glu Thr Trp Tyr Ser Lys Asp Val Val Cys Glu
130 135 140
Leu Asn Lys Thr Asp Gly Gly Arg Gly Arg Cys Tyr Met Asn His Cys
145 150 155 160
Asn Thr Ser Val Ile Thr Glu Ser Cys Asp Lys His Tyr Trp Asp Ala
165 170 175
Ile Arg Phe Arg Tyr Cys Ala Pro Pro Gly Phe Ala Leu Leu Arg Cys
180 185 190
Asn Asp Thr Asn Tyr Ser Gly Phe Met Pro Asn Cys Ser Lys Val Val
195 200 205
Val Ser Ser Cys Thr Arg Met Met Glu Thr Gln Thr Ser Thr Trp Leu
210 215 220
Gly Phe Asn Gly Thr Arg Ala Glu Asn Arg Thr Tyr Met Tyr Trp His
225 230 235 240
Ser Lys Asp Asn Arg Thr Ile Ile Ser Leu Asn Lys Tyr Tyr Asn Leu
245 250 255
Thr Met His Cys Lys Arg Pro Gly Asn Lys Thr Val Ala Pro Ile Thr
260 265 270
Leu Met Ser Gly Leu Val Phe His Ser Gln Pro Ile Asn Arg Arg Pro
275 280 285
Arg Gln Ala Trp Cys Trp Phe Lys Gly Gln Trp Arg Glu Ala Met Gln
290 295 300
Glu Val Lys Arg Thr Leu Ile Lys His Pro Arg Tyr Lys Gly Thr Asn
305 310 315 320
Asp Thr Arg Asn Ile Thr Phe Thr Lys Pro Gly Glu Gly Ser Asp Pro
325 330 335
Glu Val Ala Tyr Met Trp Thr Asn Cys Arg Gly Glu Phe Leu Tyr Cys
340 345 350
Asn Met Thr Trp Phe Leu Asn Trp Val Glu Asn Arg Thr Gly Gln Thr
355 360 365
Gln Arg Asn Tyr Ala Pro Cys His Ile Lys Gln Ile Ile Asn Thr Trp
370 375 380
His Lys Val Gly Lys Asn Val Tyr Leu Pro Pro Arg Glu Gly Glu Leu
385 390 395 400
Thr Cys Asn Ser Thr Val Thr Ser Ile Ile Ala Asn Ile Asp Val Asp
405 410 415
Ser Asn Asn Asn Arg Thr Asn Ile Thr Phe Ser Ala Glu Val Ala Glu
420 425 430
Leu Tyr Arg Leu Glu Leu Gly Asp Tyr Lys Leu Ile Glu Val Thr Val
435 440 445
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
450 455 460
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
465 470 475 480
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
485 490 495
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
500 505 510
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
515 520 525
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
530 535 540
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
545 550 555 560
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
565 570 575
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
580 585 590
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
595 600 605
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
610 615 620
Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln
625 630 635 640
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
645 650 655
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
660 665 670
Gly Ile Val Gln Gln Ile Ala Gly Asn Tyr Val His Met Pro Leu Ser
675 680 685
Pro Arg Thr Leu Asn Ala Trp Val Lys Leu Val Glu Glu Lys Lys Phe
690 695 700
Gly Ala Glu Val Val Pro Gly Phe Gln Ala Leu Ser Glu Gly Cys Thr
705 710 715 720
Pro Tyr Asp Ile Asn Gln Met Leu Asn Cys Val Gly Asp His Gln Ala
725 730 735
Ala Met Gln Ile Ile Arg Glu Ile Ile Asn Glu Glu Ala Ala Asp Trp
740 745 750
Asp Gln Gln His Pro Ile Pro Gly Pro Leu Pro Ala Gly Gln Leu Arg
755 760 765
Asp Pro Arg Gly Ser Asp Ile Ala Gly Thr Thr Ser Thr Val Glu Glu
770 775 780
Gln Ile Gln Trp Met Tyr Arg Ala Gln Asn Pro Val Pro Val Gly Asn
785 790 795 800
Ile Tyr Arg Arg Trp Ile Gln Ile Gly Leu Gln Lys Cys Val Arg Met
805 810 815
Tyr Asn Pro Thr Asn Ile Leu Asp Ile Lys Gln Gly Pro Lys Glu Pro
820 825 830
Phe Gln Ser Tyr Val Asp Arg Phe Tyr Lys Ser Leu Arg Ala Glu Gln
835 840 845
Thr Asp Pro Ala Val Lys Asn Trp Met Thr Gln Thr Leu Leu Ile Gln
850 855 860
Asn Ala Asn Pro Asp Cys Lys Leu Val Leu Lys Gly Leu Gly Met Asn
865 870 875 880
Pro Thr Leu Glu Glu Met Leu Thr Ala Cys Gln Gly Ile Gly Gly Pro
885 890 895
Gly Gln Lys Ala Arg Leu Met
900
<210> 90
<211> 10
<212> PRT
<213> 合成的
<400> 90
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys
1 5 10
<210> 91
<211> 584
<212> PRT
<213> 合成的
<400> 91
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
35 40 45
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
130 135 140
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
145 150 155 160
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Pro Glu Val Ser
195 200 205
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
210 215 220
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
225 230 235 240
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
245 250 255
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
260 265 270
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
275 280 285
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
290 295 300
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
305 310 315 320
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
325 330 335
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
340 345 350
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
355 360 365
Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys
370 375 380
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
385 390 395 400
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
405 410 415
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
420 425 430
Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile
435 440 445
Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His
450 455 460
Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Ile
465 470 475 480
Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp
485 490 495
Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala
500 505 510
Ser Trp Ser Asn Lys Ser Leu Glu Gln Ile Trp Asn His Thr Thr Trp
515 520 525
Met Glu Trp Asp Arg Glu Ile Asn Asn Tyr Thr Ser Leu Ile His Ser
530 535 540
Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu
545 550 555 560
Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr
565 570 575
Asn Trp Leu Trp Tyr Ile Lys Leu
580
<210> 92
<211> 507
<212> PRT
<213> 合成的
<400> 92
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
35 40 45
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
130 135 140
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
145 150 155 160
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
450 455 460
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
465 470 475 480
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
485 490 495
Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu
500 505
<210> 93
<211> 604
<212> PRT
<213> 合成的
<400> 93
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln
20 25 30
Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile
35 40 45
Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln
50 55 60
Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln
65 70 75 80
Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala
85 90 95
Val Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Glu Gln Ile Trp
100 105 110
Asn His Thr Thr Trp Met Glu Trp Asp Arg Glu Ile Asn Asn Tyr Thr
115 120 125
Ser Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys
130 135 140
Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn
145 150 155 160
Trp Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys Leu Gly Gly Gly
165 170 175
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe
195 200 205
Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val
210 215 220
Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe
225 230 235 240
Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro
245 250 255
Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro
260 265 270
Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val
275 280 285
Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr
290 295 300
Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys
305 310 315 320
Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp
325 330 335
Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro
340 345 350
Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser
355 360 365
Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala
370 375 380
Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His
385 390 395 400
His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly
405 410 415
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
435 440 445
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
450 455 460
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
465 470 475 480
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
485 490 495
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
500 505 510
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
515 520 525
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
530 535 540
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
545 550 555 560
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
565 570 575
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
580 585 590
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu
595 600
<210> 94
<211> 604
<212> PRT
<213> 合成的
<400> 94
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Ile Phe Arg Pro Gly Gly Gly Asn Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro
35 40 45
Leu Gly Val Ala Pro Ser Arg Ala Lys Arg Arg Val Val Glu Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Met Leu Lys Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Lys
130 135 140
Ser Met Asn Glu Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys
145 150 155 160
Glu Ile Ser Asn Tyr Thr Gln Ile Ile Tyr Asn Leu Ile Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
450 455 460
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
465 470 475 480
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
485 490 495
Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu
500 505 510
Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val
515 520 525
Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Glu Gln Ile Trp Asn
530 535 540
His Thr Thr Trp Met Glu Trp Asp Arg Glu Ile Asn Asn Tyr Thr Ser
545 550 555 560
Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
565 570 575
Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
580 585 590
Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys Leu
595 600
<210> 95
<211> 604
<212> PRT
<213> 合成的
<400> 95
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Thr Phe Arg Pro Gly Gly Gly Asn Ile Lys Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Gln Ile Glu Pro
35 40 45
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Glu Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Lys Asp Gln Gln Phe Leu Gly Leu Trp Gly Cys Ser Gly Lys
115 120 125
Ile Ile Cys Thr Thr Ala Val Pro Trp Asn Ser Thr Trp Ser Asn Arg
130 135 140
Ser Tyr Glu Glu Ile Trp Asn Asn Met Thr Trp Ile Glu Trp Glu Arg
145 150 155 160
Glu Ile Ser Asn Tyr Thr Asn Gln Ile Tyr Glu Ile Leu Thr Glu Ser
165 170 175
Gln Asp Gln Gln Asp Arg Asn Glu Lys Asp Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
450 455 460
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
465 470 475 480
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
485 490 495
Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu
500 505 510
Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val
515 520 525
Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Glu Gln Ile Trp Asn
530 535 540
His Thr Thr Trp Met Glu Trp Asp Arg Glu Ile Asn Asn Tyr Thr Ser
545 550 555 560
Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
565 570 575
Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
580 585 590
Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys Leu
595 600
<210> 96
<211> 604
<212> PRT
<213> 合成的
<400> 96
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro
35 40 45
Leu Gly Val Ala Pro Thr His Ala Lys Arg Arg Val Val Glu Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser
65 70 75 80
Asn Leu Leu Lys Ala Ile Glu Ala Gln Gln His Leu Leu Lys Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Leu Glu Arg
100 105 110
Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Thr Val Pro Trp Asn Ser Ser Trp Ser Asn Lys
130 135 140
Thr Tyr Asn Asp Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys
145 150 155 160
Glu Ile Ser Asn Tyr Thr Asn Ile Ile Tyr Asn Leu Ile Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
450 455 460
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
465 470 475 480
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
485 490 495
Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu
500 505 510
Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val
515 520 525
Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Glu Gln Ile Trp Asn
530 535 540
His Thr Thr Trp Met Glu Trp Asp Arg Glu Ile Asn Asn Tyr Thr Ser
545 550 555 560
Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn
565 570 575
Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp
580 585 590
Phe Asn Ile Thr Asn Trp Leu Trp Tyr Ile Lys Leu
595 600
<210> 97
<211> 507
<212> PRT
<213> 合成的
<400> 97
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro
35 40 45
Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Glu Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Lys Asp Gln Gln Leu Leu Gly Leu Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ser Ser Trp Ser Asn Lys
130 135 140
Ser Met Glu Asp Ile Trp Asp Asn Met Thr Trp Leu Glu Trp Asp Arg
145 150 155 160
Glu Ile Ser Asn Tyr Thr Gln Ile Ile Tyr Asn Leu Ile Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Ala Ser Met Thr Leu Thr Val Gln Ala Arg Gln Leu
450 455 460
Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu
465 470 475 480
Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu
485 490 495
Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu
500 505
<210> 98
<211> 684
<212> PRT
<213> 合成的
<400> 98
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
35 40 45
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
130 135 140
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
145 150 155 160
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Met Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val
450 455 460
His Gln Ala Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val
465 470 475 480
Glu Glu Lys Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu
485 490 495
Ser Glu Gly Ala Thr Pro Gln Asp Leu Asn Thr Met Leu Asn Thr Val
500 505 510
Gly Gly His Gln Ala Ala Met Gln Met Leu Lys Glu Thr Ile Asn Glu
515 520 525
Glu Ala Ala Glu Trp Asp Arg Val His Pro Val His Ala Gly Pro Ile
530 535 540
Ala Pro Gly Gln Met Arg Glu Pro Arg Gly Ser Asp Ile Ala Gly Thr
545 550 555 560
Thr Ser Thr Leu Gln Glu Gln Ile Gly Trp Met Thr Asn Asn Pro Pro
565 570 575
Ile Pro Val Gly Glu Ile Tyr Lys Arg Trp Ile Ile Leu Gly Leu Asn
580 585 590
Lys Ile Val Arg Met Tyr Ser Pro Thr Ser Ile Leu Asp Ile Arg Gln
595 600 605
Gly Pro Lys Glu Pro Phe Arg Asp Tyr Val Asp Arg Phe Tyr Lys Thr
610 615 620
Leu Arg Ala Glu Gln Ala Ser Gln Asp Val Lys Asn Trp Met Thr Glu
625 630 635 640
Thr Leu Leu Val Gln Asn Ala Asn Pro Asp Cys Lys Thr Ile Leu Lys
645 650 655
Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu Met Met Thr Ala Cys Gln
660 665 670
Gly Val Gly Gly Pro Gly His Lys Ala Arg Val Leu
675 680
<210> 99
<211> 684
<212> PRT
<213> 合成的
<400> 99
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val
20 25 30
His Gln Ala Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val
35 40 45
Glu Glu Lys Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu
50 55 60
Ser Glu Gly Ala Thr Pro Gln Asp Leu Asn Thr Met Leu Asn Thr Val
65 70 75 80
Gly Gly His Gln Ala Ala Met Gln Met Leu Lys Glu Thr Ile Asn Glu
85 90 95
Glu Ala Ala Glu Trp Asp Arg Val His Pro Val His Ala Gly Pro Ile
100 105 110
Ala Pro Gly Gln Met Arg Glu Pro Arg Gly Ser Asp Ile Ala Gly Thr
115 120 125
Thr Ser Thr Leu Gln Glu Gln Ile Gly Trp Met Thr Asn Asn Pro Pro
130 135 140
Ile Pro Val Gly Glu Ile Tyr Lys Arg Trp Ile Ile Leu Gly Leu Asn
145 150 155 160
Lys Ile Val Arg Met Tyr Ser Pro Thr Ser Ile Leu Asp Ile Arg Gln
165 170 175
Gly Pro Lys Glu Pro Phe Arg Asp Tyr Val Asp Arg Phe Tyr Lys Thr
180 185 190
Leu Arg Ala Glu Gln Ala Ser Gln Asp Val Lys Asn Trp Met Thr Glu
195 200 205
Thr Leu Leu Val Gln Asn Ala Asn Pro Asp Cys Lys Thr Ile Leu Lys
210 215 220
Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu Met Met Thr Ala Cys Gln
225 230 235 240
Gly Val Gly Gly Pro Gly His Lys Ala Arg Val Leu Gly Gly Gly Gly
245 250 255
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
260 265 270
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
275 280 285
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
290 295 300
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
305 310 315 320
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
325 330 335
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
340 345 350
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
355 360 365
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
370 375 380
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
385 390 395 400
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
405 410 415
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
420 425 430
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
435 440 445
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
450 455 460
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
465 470 475 480
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
485 490 495
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Gly Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
515 520 525
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
530 535 540
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
545 550 555 560
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
565 570 575
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
580 585 590
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
595 600 605
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
610 615 620
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
625 630 635 640
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
645 650 655
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
660 665 670
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu
675 680
<210> 100
<211> 642
<212> PRT
<213> 合成的
<400> 100
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
35 40 45
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
130 135 140
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
145 150 155 160
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Met Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val
450 455 460
His Gln Ala Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val
465 470 475 480
Glu Glu Lys Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu
485 490 495
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
500 505 510
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Gln Met Leu Lys Glu
515 520 525
Thr Ile Asn Glu Glu Ala Ala Glu Trp Asp Arg Val His Pro Val His
530 535 540
Ala Gly Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
545 550 555 560
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Ser Gln
565 570 575
Asp Val Lys Asn Trp Met Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly
580 585 590
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
595 600 605
Cys Lys Thr Ile Leu Lys Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu
610 615 620
Met Met Thr Ala Cys Gln Gly Val Gly Gly Pro Gly His Lys Ala Arg
625 630 635 640
Val Leu
<210> 101
<211> 642
<212> PRT
<213> 合成的
<400> 101
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val
20 25 30
His Gln Ala Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val
35 40 45
Glu Glu Lys Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu
50 55 60
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Gln Met Leu Lys Glu
85 90 95
Thr Ile Asn Glu Glu Ala Ala Glu Trp Asp Arg Val His Pro Val His
100 105 110
Ala Gly Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Ser Gln
130 135 140
Asp Val Lys Asn Trp Met Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly
145 150 155 160
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
165 170 175
Cys Lys Thr Ile Leu Lys Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu
180 185 190
Met Met Thr Ala Cys Gln Gly Val Gly Gly Pro Gly His Lys Ala Arg
195 200 205
Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Pro Glu Val Ser
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
245 250 255
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
260 265 270
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
275 280 285
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
290 295 300
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
340 345 350
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
355 360 365
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
370 375 380
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
385 390 395 400
Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys
405 410 415
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
420 425 430
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
435 440 445
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
450 455 460
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Val Phe Arg Pro Gly
465 470 475 480
Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys
485 490 495
Val Ile Lys Ile Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg
500 505 510
Arg Val Val Gln Arg Glu Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly
515 520 525
Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln
530 535 540
His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg
545 550 555 560
Val Leu Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile
565 570 575
Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn
580 585 590
Ala Ser Trp Ser Asn Lys Ser Leu Glu Asp Ile Trp Asp Asn Met Thr
595 600 605
Trp Met Gln Trp Glu Arg Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr
610 615 620
Thr Leu Leu Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu
625 630 635 640
Leu Leu
<210> 102
<211> 684
<212> PRT
<213> 合成的
<400> 102
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
35 40 45
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
130 135 140
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
145 150 155 160
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Met Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val
450 455 460
His Gln Ala Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val
465 470 475 480
Glu Glu Lys Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu
485 490 495
Ser Gln Gly Ala Thr Pro Gln Glu Val Asn Thr Val Leu Asn Thr Gln
500 505 510
Gly Gly His Gln Ala Ala Met Gln Met Leu Lys Glu Thr Ile Asn Glu
515 520 525
Glu Ala Ala Glu Trp Asp Arg Val His Pro Val His Ala Gly Pro Val
530 535 540
Ala Pro Gly Gln Val Lys Asp Pro Lys Gly Ser Glu Val Ala Gly Thr
545 550 555 560
Thr Ser Thr Val Gln Asp Gln Met Gly Trp Ile Thr Asn Asn Pro Pro
565 570 575
Val Pro Ile Gly Asn Val Gln Arg Lys Trp Ile Val Val Gly Val Asn
580 585 590
Arg Val Val Lys Val Tyr Ser Pro Thr Ser Val Leu Asp Val Lys Gln
595 600 605
Gly Pro Arg Asp Pro Phe Arg Glu Tyr Ile Glu Lys Phe Tyr Arg Thr
610 615 620
Leu Lys Ala Ser Gln Ala Ser Gln Asp Val Lys Asn Trp Met Thr Asp
625 630 635 640
Thr Val Val Ile Gln Asn Ala Asn Pro Glu Cys Lys Thr Ile Leu Lys
645 650 655
Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu Met Met Thr Ala Cys Gln
660 665 670
Gly Val Gly Gly Pro Gly His Lys Ala Arg Val Leu
675 680
<210> 103
<211> 684
<212> PRT
<213> 合成的
<400> 103
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val
20 25 30
His Gln Ala Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val
35 40 45
Glu Glu Lys Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu
50 55 60
Ser Gln Gly Ala Thr Pro Gln Glu Val Asn Thr Val Leu Asn Thr Gln
65 70 75 80
Gly Gly His Gln Ala Ala Met Gln Met Leu Lys Glu Thr Ile Asn Glu
85 90 95
Glu Ala Ala Glu Trp Asp Arg Val His Pro Val His Ala Gly Pro Val
100 105 110
Ala Pro Gly Gln Val Lys Asp Pro Lys Gly Ser Glu Val Ala Gly Thr
115 120 125
Thr Ser Thr Val Gln Asp Gln Met Gly Trp Ile Thr Asn Asn Pro Pro
130 135 140
Val Pro Ile Gly Asn Val Gln Arg Lys Trp Ile Val Val Gly Val Asn
145 150 155 160
Arg Val Val Lys Val Tyr Ser Pro Thr Ser Val Leu Asp Val Lys Gln
165 170 175
Gly Pro Arg Asp Pro Phe Arg Glu Tyr Ile Glu Lys Phe Tyr Arg Thr
180 185 190
Leu Lys Ala Ser Gln Ala Ser Gln Asp Val Lys Asn Trp Met Thr Asp
195 200 205
Thr Val Val Ile Gln Asn Ala Asn Pro Glu Cys Lys Thr Ile Leu Lys
210 215 220
Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu Met Met Thr Ala Cys Gln
225 230 235 240
Gly Val Gly Gly Pro Gly His Lys Ala Arg Val Leu Gly Gly Gly Gly
245 250 255
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
260 265 270
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
275 280 285
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
290 295 300
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
305 310 315 320
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
325 330 335
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
340 345 350
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
355 360 365
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
370 375 380
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
385 390 395 400
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
405 410 415
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
420 425 430
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
435 440 445
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
450 455 460
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
465 470 475 480
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
485 490 495
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Gly Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
515 520 525
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
530 535 540
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
545 550 555 560
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
565 570 575
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
580 585 590
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
595 600 605
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
610 615 620
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
625 630 635 640
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
645 650 655
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
660 665 670
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu
675 680
<210> 104
<211> 684
<212> PRT
<213> 合成的
<400> 104
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
20 25 30
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
35 40 45
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
50 55 60
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
65 70 75 80
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
85 90 95
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
100 105 110
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
115 120 125
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
130 135 140
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
145 150 155 160
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
165 170 175
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Gly Gly Gly Gly
180 185 190
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
195 200 205
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
210 215 220
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
225 230 235 240
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
245 250 255
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
260 265 270
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
275 280 285
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
290 295 300
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
305 310 315 320
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
325 330 335
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
340 345 350
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
355 360 365
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
370 375 380
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
385 390 395 400
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
405 410 415
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
420 425 430
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
435 440 445
Gly Gly Gly Ser Met Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val
450 455 460
His Gln Ala Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val
465 470 475 480
Glu Glu Lys Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu
485 490 495
Ser Ala Gly Ala Thr Pro Ala Ala Ala Asn Thr Ala Leu Asn Thr Ala
500 505 510
Gly Gly His Gln Ala Ala Met Gln Met Leu Lys Glu Thr Ile Asn Glu
515 520 525
Glu Ala Ala Glu Trp Asp Arg Val His Pro Val His Ala Gly Pro Ala
530 535 540
Ala Pro Gly Ala Ala Ala Ala Pro Ala Gly Ser Ala Ala Ala Gly Thr
545 550 555 560
Thr Ser Thr Ala Gln Ala Gln Ala Gly Trp Ala Thr Asn Asn Pro Pro
565 570 575
Ala Pro Ala Gly Ala Ala Ala Ala Ala Trp Ile Ala Ala Gly Ala Asn
580 585 590
Ala Ala Val Ala Ala Tyr Ser Pro Thr Ser Ala Leu Asp Ala Ala Ala
595 600 605
Gly Pro Ala Ala Pro Phe Arg Ala Ala Ala Ala Ala Phe Tyr Ala Thr
610 615 620
Leu Ala Ala Ala Gln Ala Ser Gln Asp Val Lys Asn Trp Met Thr Ala
625 630 635 640
Thr Ala Ala Ala Ala Asn Ala Asn Pro Ala Cys Lys Thr Ile Leu Lys
645 650 655
Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu Met Met Thr Ala Cys Gln
660 665 670
Gly Val Gly Gly Pro Gly His Lys Ala Arg Val Leu
675 680
<210> 105
<211> 684
<212> PRT
<213> 合成的
<400> 105
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Met Pro Ile Val Gln Asn Leu Gln Gly Gln Met Val
20 25 30
His Gln Ala Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys Val Val
35 40 45
Glu Glu Lys Ala Phe Ser Pro Glu Val Ile Pro Met Phe Ser Ala Leu
50 55 60
Ser Ala Gly Ala Thr Pro Ala Ala Ala Asn Thr Ala Leu Asn Thr Ala
65 70 75 80
Gly Gly His Gln Ala Ala Met Gln Met Leu Lys Glu Thr Ile Asn Glu
85 90 95
Glu Ala Ala Glu Trp Asp Arg Val His Pro Val His Ala Gly Pro Ala
100 105 110
Ala Pro Gly Ala Ala Ala Ala Pro Ala Gly Ser Ala Ala Ala Gly Thr
115 120 125
Thr Ser Thr Ala Gln Ala Gln Ala Gly Trp Ala Thr Asn Asn Pro Pro
130 135 140
Ala Pro Ala Gly Ala Ala Ala Ala Ala Trp Ile Ala Ala Gly Ala Asn
145 150 155 160
Ala Ala Val Ala Ala Tyr Ser Pro Thr Ser Ala Leu Asp Ala Ala Ala
165 170 175
Gly Pro Ala Ala Pro Phe Arg Ala Ala Ala Ala Ala Phe Tyr Ala Thr
180 185 190
Leu Ala Ala Ala Gln Ala Ser Gln Asp Val Lys Asn Trp Met Thr Ala
195 200 205
Thr Ala Ala Ala Ala Asn Ala Asn Pro Ala Cys Lys Thr Ile Leu Lys
210 215 220
Ala Leu Gly Pro Ala Ala Thr Leu Glu Glu Met Met Thr Ala Cys Gln
225 230 235 240
Gly Val Gly Gly Pro Gly His Lys Ala Arg Val Leu Gly Gly Gly Gly
245 250 255
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
260 265 270
Gly Gly Gly Gly Ser Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
275 280 285
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
290 295 300
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
305 310 315 320
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
325 330 335
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
340 345 350
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
355 360 365
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
370 375 380
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
385 390 395 400
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
405 410 415
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
420 425 430
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
435 440 445
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
450 455 460
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
465 470 475 480
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser
485 490 495
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Gly Ser Met Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp
515 520 525
Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro
530 535 540
Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu
545 550 555 560
Lys Arg Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn
565 570 575
Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr
580 585 590
Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg
595 600 605
Tyr Leu Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys
610 615 620
Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys
625 630 635 640
Ser Leu Glu Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg
645 650 655
Glu Ile Asp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser
660 665 670
Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu
675 680
<210> 106
<211> 800
<212> PRT
<213> 合成的
<400> 106
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu
20 25 30
Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val
35 40 45
Gln Ala Arg Asn Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu
50 55 60
Leu Arg Ala Pro Glu Ala Gln Gln His Leu Leu Lys Leu Thr Val Trp
65 70 75 80
Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu
85 90 95
Arg Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile
100 105 110
Cys Cys Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Arg Asn Leu
115 120 125
Ser Glu Ile Trp Asp Asn Met Thr Trp Leu Gln Trp Asp Lys Glu Ile
130 135 140
Ser Asn Tyr Thr Gln Ile Ile Tyr Gly Leu Leu Glu Glu Ser Gln Asn
145 150 155 160
Gln Gln Glu Lys Asn Glu Gln Asp Leu Leu Ala Leu Asp Lys Trp Ala
165 170 175
Ser Leu Trp Asn Trp Phe Asp Ile Thr Asn Trp Leu Trp Tyr Ile Gln
180 185 190
Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys
195 200 205
Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val
210 215 220
Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe
225 230 235 240
Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu
245 250 255
Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His
260 265 270
Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys
275 280 285
Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser
290 295 300
Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met
305 310 315 320
Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro
325 330 335
Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn
340 345 350
Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met
355 360 365
Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser
370 375 380
Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr
385 390 395 400
Lys Ser Phe Ser Arg Thr Pro Gly Lys Ala Glu Ala Ala Ala Lys Glu
405 410 415
Ala Ala Ala Lys Ala Ala Trp Glu Asp Ala Asp Thr Thr Leu Phe Cys
420 425 430
Ala Ser Asp Ala Lys Ala Tyr Ser Thr Glu Lys His Asn Val Trp Ala
435 440 445
Thr His Ala Cys Val Pro Thr Asp Pro Asp Pro Gln Glu Ile Pro Leu
450 455 460
Glu Asn Val Thr Glu Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu
465 470 475 480
Gln Met His Glu Asp Ile Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro
485 490 495
Cys Val Met Leu Thr Gly Gly Ser Thr Ile Lys Gln Ala Cys Pro Lys
500 505 510
Val Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe
515 520 525
Ala Ile Leu Lys Cys Arg Asp Glu Asp Phe Asn Gly Thr Gly Pro Cys
530 535 540
Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val
545 550 555 560
Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Lys Gly Asp Ile Val
565 570 575
Ile Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Val Ile Ile Val Gln
580 585 590
Leu Asn Glu Pro Val Gln Ile Val Cys Ile Arg Pro Asn Asn Gly Gly
595 600 605
Ser Gly Ser Gly Gly Asp Ile Arg Gln Ala His Cys Asn Val Thr Arg
610 615 620
Ser Arg Trp Asn Lys Thr Leu Gln Glu Val Lys Glu Gln Leu Trp Lys
625 630 635 640
Ile Phe Asn Lys Thr Thr Asn Ile Thr Phe Asn Asn Thr Ile Phe Asn
645 650 655
Ser Pro Ala Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn Cys
660 665 670
Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asp Leu Phe Asn Glu Thr
675 680 685
Asn Leu Ser Ala Asn His Thr Asp Thr Asn Glu Asn Ile Thr Leu Gln
690 695 700
Cys Arg Ile Lys Gln Ile Val Arg Met Trp Gln Arg Val Gly Gln Ala
705 710 715 720
Met Tyr Ala Pro Pro Ile Ala Gly Asn Ile Thr Cys Ile Ser Asn Ile
725 730 735
Thr Gly Leu Leu Leu Thr Arg Asp Gly Val Asn Asp Thr His Asp Lys
740 745 750
Glu Asn Glu Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp Asn Trp
755 760 765
Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Ile Asn Phe
770 775 780
Ala Asn Ser Thr Gly Gly Asp Leu Glu Ile Thr Thr His Ser Phe Asn
785 790 795 800
<210> 107
<211> 226
<212> PRT
<213> 合成的
<400> 107
Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu
1 5 10 15
Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr
20 25 30
Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys
35 40 45
Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val
50 55 60
His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe
65 70 75 80
Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val
115 120 125
Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser
130 135 140
Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu
145 150 155 160
Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro
165 170 175
Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val
180 185 190
Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu
195 200 205
His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser
210 215 220
Pro Gly
225
<210> 108
<211> 13
<212> PRT
<213> 合成的
<400> 108
Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr
1 5 10
<210> 109
<211> 15
<212> PRT
<213> 合成的
<400> 109
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 110
<211> 25
<212> PRT
<213> 合成的
<400> 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser
20 25
<210> 111
<211> 5
<212> PRT
<213> 合成的
<400> 111
Gly Gly Gly Pro Ser
1 5

Claims (32)

1.一种重组多肽,所述重组多肽包含
前导肽,
融合蛋白,
HIV gp120蛋白的至少一个表位,和/或
HIV gp41蛋白的至少一个表位;
其中所述融合蛋白包含不由HIV编码的区域,所述区域选自由以下组成的组:抗体的Fc结构域、p53结构域、GCN4结构域或网格蛋白结构域,并且
其中所述重组多肽缺少跨膜结构域。
2.如权利要求1所述的重组多肽,其中所述跨膜结构域的氨基酸序列选自由以下组成的组:SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ IDNO:68、SEQ ID NO:69、SEQ ID NO:70、SEQ ID NO:71或SEQ ID NO:72。
3.如权利要求1或2中任一项所述的重组多肽,其中所述重组多肽包含至少4个、5个、6个、7个、8个、9个或10个表位。
4.如权利要求3所述的重组多肽,其中每个表位通过接头被连接至另一个表位,所述接头的氨基酸序列不由HIV编码。
5.如权利要求4所述的重组多肽,其中将每个表位连接至另一个表位的所述接头包含以下中列出的氨基酸序列:SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:109、SEQ ID NO:110或SEQ ID NO:111。
6.如前述权利要求中任一项所述的重组多肽,其中所述重组多肽包含以下中列出的氨基酸序列:SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ IDNO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ IDNO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ IDNO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ IDNO:91、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ IDNO:97、SEQ ID NO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQID NO:103、SEQ ID NO:104、SEQ ID NO:105或SEQ ID NO:106。
7.如权利要求1至5中任一项所述的重组多肽,其中所述融合蛋白包含抗体Fc结构域,所述抗体Fc结构域的氨基酸序列选自由以下组成的组:SEQ ID.NO:77、SEQ ID.NO:78、SEQID.NO:80或SEQ ID.NO:107。
8.如权利要求7所述的重组多肽,其中
所述抗体Fc结构域缺少寡聚化结构域;并且
所述重组多肽是单体。
9.如权利要求8所述的重组多肽,其中所述重组多肽包含以下中列出的氨基酸序列:SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ IDNO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:91、SEQ IDNO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ ID NO:97、SEQ IDNO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105或SEQ ID NO:106。
10.如权利要求7所述的重组多肽,其中所述抗体Fc结构域包括二聚化结构域。
11.如权利要求10所述的重组多肽,其中所述重组多肽包含以下中列出的氨基酸序列:SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17或SEQ ID NO:19。
12.如权利要求1至5或10至11中任一项所述的重组多肽,其中所述融合蛋白包含选自由p53结构域、GCN4结构域、网格蛋白结构域或抗体的Fc结构域组成的组的寡聚化结构域。
13.如权利要求12所述的重组多肽,其中所述重组多肽包含以下中列出的氨基酸序列:SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:9、SEQID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17或SEQ ID NO:19。
14.如前述权利要求中任一项所述的重组多肽,其中
所述重组多肽的N-末端由所述前导肽组成;并且
所述前导肽能够在多肽在哺乳动物细胞中翻译后将所述重组多肽移位到所述哺乳动物细胞的细胞膜表面的外部。
15.如前述权利要求中任一项所述的重组多肽,其中所述前导肽包含SEQ ID NO:84中列出的氨基酸序列。
16.如权利要求14或15中任一项所述的重组多肽,其中
所述融合蛋白是所述前导肽;
所述重组多肽包含HIV gp120的表位和HIV gp41的表位;并且
所述重组多肽缺少gp120/gp41裂解位点。
17.如权利要求16所述的重组多肽,其中所述重组多肽包含以下中列出的氨基酸序列:SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:38。
18.如前述权利要求中任一项所述的重组多肽,其中所述重组多肽还包含多组氨酸亲和标签。
19.一种寡聚多肽,所述寡聚多肽包含至少两个根据权利要求1至7和10至18中任一项所述的重组多肽。
20.一种核酸,所述核酸包含:
核苷酸序列,所述核苷酸序列编码权利要求1-18中任一项所述的多肽或权利要求19所述的寡聚多肽;和
启动子,所述启动子可操作地连接至所述核苷酸序列。
21.一种细胞,所述细胞包含核酸,所述核酸包含编码权利要求1至18中任一项所述的多肽或权利要求19所述的寡聚多肽的核苷酸序列,其中所述细胞是哺乳动物细胞。
22.如权利要求21所述的细胞,其中所述细胞是CHO、BHK、NS0、Sp2/0、COS、C127、HEK293、HT-1080、PER.C6、HeLa或Jurkat细胞。
23.一种免疫测定试剂,所述免疫测定试剂包含根据权利要求1至18中任一项所述的多肽或权利要求19所述的寡聚多肽,其中所述免疫测定试剂结合至固体支持物。
24.如权利要求23所述的免疫测定试剂,其中所述固体支持物是珠、膜、微量滴定板、多肽芯片或色谱柱的固相。
25.一种用于测定包含HIV抗体的组合物的装置,所述装置包括固体支持物和权利要求1至18中任一项所述的多肽或权利要求19所述的寡聚多肽,其中所述寡聚多肽共价地或非共价地结合至所述固体支持物。
26.如权利要求25所述的装置,其中所述固体支持物是珠、膜、微量滴定板、多肽芯片或色谱柱的固相。
27.一种测定包含抗体的样品的方法,所述方法包括:
使所述样品与权利要求1至18中任一项所述的多肽或权利要求19所述的寡聚多肽接触;和
确定所述抗体和所述多肽或所述寡聚多肽之间的结合亲和力。
28.如权利要求27所述的方法,其中:
所述结合亲和力是相对结合亲和力;并且
所述结合亲和力是相对结合亲和力是因为它是相对于一种或更多种不同抗体的结合亲和力。
29.一种产生抗体的方法,所述方法包括向动物施用权利要求1至18中任一项所述的多肽或权利要求19所述的寡聚多肽。
30.一种从多于一种抗体中选择抗HIV抗体的方法,所述方法包括:
使(a)权利要求1至18中任一项所述的多肽或权利要求19所述的寡聚多肽与(b)包含所述多于一种抗体的组合物接触;和
鉴定相对于所述组合物中的其他抗体对所述多肽或所述寡聚多肽具有高结合亲和力的抗体,从而选择所述抗HIV抗体。
31.一种预防或治疗人类患者中的HIV感染的方法,所述方法包括向所述患者施用权利要求1至18中任一项所述的多肽或权利要求19所述的寡聚多肽。
32.一种从人类生物样品的供应物选择生物样品的方法,所述方法包括从所述供应物选择不包含与权利要求1至18中任一项所述的多肽或权利要求19所述的寡聚多肽形成抗原-抗体复合物的抗体的那些样品。
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