CN114258399A - 蛋白质容器、多核苷酸、载体、表达盒、细胞、容器的生产方法、病原体识别或疾病诊断方法、容器的用途、和诊断试剂盒 - Google Patents
蛋白质容器、多核苷酸、载体、表达盒、细胞、容器的生产方法、病原体识别或疾病诊断方法、容器的用途、和诊断试剂盒 Download PDFInfo
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Abstract
本发明涉及一种蛋白质容器,可向其同时插入各种外源多氨基酸序列用于在各种系统中表达和用于各种用途。本发明涉及可产生上述提及的蛋白质容器的多核苷酸。本发明还涉及包括上述提及的多核苷酸的载体和表达盒。本发明还涉及包括上述提及的载体或表达盒的细胞。本发明还涉及用于生产所述蛋白质容器和识别病原体或体外诊断疾病的方法。本发明还涉及所述蛋白质容器和包括所述蛋白质容器的试剂盒用于诊断或作为疫苗组合物的用途。
Description
技术领域
本发明落入化学、药学、医学、生物技术的应用领域,更具体地,在用于生物医药目的的制剂的领域内。本发明涉及可伴随地接受多条外源多氨基酸序列的蛋白质容器(protein receptacle),用于在各种系统中表达和用于不同用途。本发明涉及可产生上述提及的蛋白质容器的多核苷酸。本发明还涉及包含前述多核苷酸(一种或多种)的载体和表达盒。本发明进一步涉及包含前述载体或表达盒的细胞。本发明进一步涉及用于生产所述蛋白质容器和用于病原体识别或体外疾病诊断的方法。本发明进一步涉及所述蛋白质容器和包含所述蛋白质容器的试剂盒用于诊断目的或作为疫苗组合物的用途。
背景技术
本文在整个文本中有多个参考文献,其在括号中示出。这些参考文献中公开的信息包含在本文中以更好的描述本发明所属领域的现有技术。
由刺胞动物水母(Aequorea victoria,维多利亚多管发光水母)所产生的绿色荧光蛋白(GFP)在可见光谱的绿色区中发射高荧光(Prasher等,Gene 15,111(2):229-33,1992(1]),并且,经典地用作基因表达和定位的标记物,因此被认为是报告蛋白。在首次观察到GFP蛋白可发射荧光后,描述了所述蛋白的几种用途。
对于GFP作为报告蛋白的使用已针对不同用途和在不同系统中获得专利。专利申请US2018298058使用GFP作为蛋白质生产和纯化系统。专利申请CN108303539使用GFP作为用于癌症检测试验的内参(input);申请CN108220313提出了高通量GFP融合和表达方法。申请CN108192904请求保护了可将其自身插入生物膜的GFP融合蛋白;申请CN107703219已强调GFP在间充质细胞的代谢组学研究中的使用。此外,专利申请US2018016310提出了“超级折叠(superfolder)”融合GFP的变体。存在几个专利,例如具有突变的GFP以增加荧光表达或修饰荧光波长峰的这些实例:US6054321、US6096865、US6027881、US6025485。因此,很明显的是,自GFP蛋白的描述以来,GFP蛋白已作为报告蛋白的各种用途被使用并获得专利。
报告分子通常用于生物系统以监测基因表达。GFP蛋白通过免除任何底物或辅因子的使用,即其不需要像大部分其它报告蛋白一样添加任何其它试剂以可视化,而在这种情况下带来巨大的创新。GFP表现的另一优点是其显示自体荧光的能力,不需要荧光标记物。出于各种原因,荧光标记物对于其用途而言不具有适当的灵敏度或特异性。
鉴于其可自我生产可检测的绿色荧光的这一特性,GFP已广泛用于研究基因表达和蛋白质定位,并且认为其是文献中最有前途的报告蛋白之一。
在其作为报告蛋白的使用中,可在融合蛋白的生产中采用编码GFP的基因,即,将感兴趣的特定基因融合至编码GFP的基因。可将融合基因盒插入至活系统(living system)中,允许融合基因的表达和感兴趣的蛋白的细胞内定位的监测(Santos-Beneit&Errington,Archives Microbiology,199(6):875-880,2017;Belardinelli&Jackson,Tuberculosis(Edinb),105:13-17,2017;Wakabayashi等,International Journal FoodMicrobiology,19,291:144-150,2018;Caì等,Viruses,20;10(11),2018)。
在酵母和哺乳动物细胞系统二者中,还将GFP蛋白用作用于肽展示或甚至肽文库的框架(Kamb等,Proc.Natl.Acad Sci.USA,95:7508-7513,1998;WO 2004005322)。作为用于随机肽的展示的框架蛋白的GFP蛋白可用于定义肽文库的特性。
新GFP变体的开发中的进展寻求实现蛋白质的性质中的改进,以产生用于广泛研究目的的新试剂。通过突变,开发了新形式的GFP,其包含为了在人细胞系统中提高的生产而优化的DNA序列,即,人源化GFP蛋白(Cormack,等,Gene 173,33-38,1996;Haas,等,Current Biology 6,315-324,1996;Yang,等,核酸s Research 24,4592-4593,1996)。
在这些形式之一中,描述了增强型绿色荧光蛋白,“enhanced green fluorescentprotein”(eGFP)(Heim&Cubitt,Nature,373,pp.663-664,1995)
起源于刺胞动物水母(维多利亚多管发光水母)的、由gfp10基因编码的GFP是238个氨基酸的蛋白质。所述蛋白质具有吸收蓝光(具有395nm处的主激发峰)并从蛋白质的中心中的生色团发射绿光(509nm处的主发射峰)的能力(Morin&Hastings,Journal CellPhysiology,77(3):313-8,1971;Prasher等,Gene 15,111(2):229-33,1992)。生色团由六肽构成,起始于氨基酸64,通过丝氨酸、酪氨酸和甘氨酸(位置65、66和67处)的环化和氧化而由一级氨基酸序列衍生(Shimomura,104(2),1979;Cody等,Biochemistry,32(5):1212-8,1993)。由GFP发射的光不依赖于表达它的细胞生物学物种并且不需要来自维多利亚多管发光水母的任何种类的底物、辅因子或其它基因产物(Chalfie等,Science,263(5148):802-5,1994)。GFP的这一性质允许其荧光在维多利亚多管发光水母以外的其它活细胞中被检测到,这是由于其可在细胞的蛋白质表达系统中被加工(Ormo等,Science 273:1392-1395,1996;Yang等,Nature Biotech 14:1246-1251,1996)。
GFP的基础结构由11条反向平行的折叠的β链组成,所述β链缠绕以形成呈β桶形状的三级结构。每条链通过一个环结构域连接到下一条链,该环结构域投射(project)到桶的上、下表面,与环境相互作用。按照惯例,各链和环都可通过编号来识别,以便更好的描述蛋白质。
定向突变实验显示GFP蛋白的某些生物化学性质由该桶结构引起。因此,一级结构中的氨基酸改变是加速蛋白质折叠、减少翻译产物的聚集、和增加溶液中蛋白质的稳定性的原因。
特定环移动至蛋白质桶的空腔,形成α螺旋,其是蛋白质的荧光性质的原因(Crone等,GFP-Based Biosensors,InTech,2013)。蛋白质结构中的一些干预可干扰发射荧光的能力。某些氨基酸中的突变可从荧光发射的强度到波长进行改变,从而改变发光颜色。作为参与荧光生色团的内部残基的Tyr66的突变可产生大量的具有改变的生色团或周围环境的结构的荧光蛋白变体。这些改变干扰不同波长下的光的吸收和发射,产生大范围的不同的发光颜色(Heim&Tsien,Current Biology,6(2):178-82,1996)。
pH的变化也可干扰荧光强度。在生理学pH下,GFP在395nm处表现最大吸收,而其在475nm处吸收较少的光。然而,将pH提高至约12.0导致最大吸收出现在475nm范围内,而其在395nm处具有减少的吸收(Ward等,Photochemistry and Photobiology,35(6):803-808,1982)。
核心蛋白的紧凑结构使GFP即使在例如由蛋白酶处理等不良条件下也高度稳定,使得该蛋白质通常作为报告蛋白而非常有用。
已存在不同形式的GFP,但总是寻求通过添加新的功能或去除一些限制来改进蛋白质。eGFP自身呈现为增强型的,其在面对F64L和S65T氨基酸的修饰时使蛋白质具有更好的灵活性(flexibility)(Heim等,Nature 373:663-664,1995;Li等,Journal BiologyChemistry,272(45):28545-9,1997)。即使当其蛋白质序列中具有异源序列的情况下,该增强允许GFP兼顾实现其预期的三维形状以及其表达荧光的能力(Pedelacq等,NatBiotechnology,24(1):79-88,2006)。
GFAb是在两个环结构域中接受外源序列的蛋白修饰形式。在其开发中,需要几轮定向进化以选择支持外源肽插入至两个近侧区(proximal region)(即Glu-172-Asp-173和Asp-102-Asp-103)的三种突变的蛋白质克隆。作者使用未突变的蛋白质证明两条外源肽的插入阻止酵母细胞表面上的GFP荧光生产和蛋白质表达。在一系列的突变和选择后,在仅两个区域中的同时插入是可能的,但仍导致极大丧失GFP的固有活性,有时使其插入物的生产或表达变为不可能(Pavoor等,PNAS 106(29):11895-11900,2009)。
N-和C-末端环状排列的突变还表明,eGFP可在编码序列中操作而不影响核心蛋白的结构方面(Topell等,FEBS Letters 457(2):283-289,1999)。然而,对20种环状排列的蛋白质变体的分析表明了蛋白质对新末端的插入的耐受性(tolerance)低,以及在多数情况下,它们丧失形成生色团的能力。该事实表明,蛋白质序列的操作可强烈干扰其特性或甚至其细胞表达。
已进行某些尝试以将多个表位同时插入至GFP的环区域,目的在于实现蛋白质用于靶特异性结合反应的用途。然而,鉴于GFP及其生色团的结构敏感性,所有这些努力都显示了有限的成功。
GFP蛋白的其它突变蛋白显示发射其它类型的荧光光谱的改进形式。例如,Heim等(Proc Natl Acad Sci USA,91(26):12501-4,1994)描述了通过在氨基酸66处含有组氨酸代替酪氨酸而发射蓝色荧光的突变蛋白。其后,Heim等(Nature,373(6516):663-4,1995)还描述了突变GFP蛋白,其通过在氨基酸65处由苏氨酸取代丝氨酸而具有类似于获得自海洋动物海肾(Renilla reniformis)的光谱,每单体的消光系数是来自多管水母属(Aequorea)的天然GFP的波长峰的10倍以上。其它专利文献描述了显示例如蓝色、红色等除绿色以外的其它光发射光谱的突变GFP蛋白(US 5625048,WO 2004005322)。
此外,其它GFP突变蛋白具有优化的激发光谱,特别地用于某些氩激光流式细胞仪(FACS)设备中(US 5804387)。仍有修饰以更好地在植物细胞系统中表达的突变GFP蛋白的描述(WO1996027675)。专利文献US5968750提出了已适应于在包括人的哺乳动物细胞中表达的人源化GFP。人源化GFP将用于阅读的偏好密码子(preferential codon)整合到人细胞基因表达系统。
在现有技术中,显然如上述列出的专利文献中可看出,GFP能够在其5’或3’端包含基因而不干扰表达、三维缠结(three dimensional tangling)、和荧光产生。此外,GFP已用作用于体内肽展示或甚至肽文库的载体。在肽文库的情况中,GFP可协助随机肽的展示,并由此协助定义肽文库的特征(Kamb等,Proc.Natl.Acad.Sci.USA,95:7508-7513,1998;WO2004005322)。
例如,Abedi等(1998,Nucleic Acids Res.26:623-300)将肽插入至维多利亚多管发光水母的GFP蛋白中暴露的环的区域中,表明当在酵母和大肠杆菌(Escherichia coli)中表达时,GFP分子保留自体荧光。作者进一步阐明,GFP框架的荧光可用于监测肽的多样性、以及指定细胞中指定肽的存在或表达。然而,与天然GFP相比,GFP框架分子的荧光率相对低。Kamb和Abedi(US 6025485)从增强型绿色荧光蛋白(eGFP)制备GFP阵列的文库以增强荧光强度。
此外,Peele等(Chem.&Bio.8:521-534,2001)在哺乳动物细胞中使用eGFP作为框架试验了具有不同结构性偏差的肽文库。Anderson等进一步通过将肽插入具有四甘氨酸配体的GFP环以增强荧光强度(US20010003650)。Happe等描述了人源化GFP,其可在哺乳动物细胞系统中大量表达,耐受肽插入、并维持自体荧光(WO 2004005322)。
然而,本技术领域中仍需要不仅展示合适的强度的荧光,并且还在细胞系统中以高水平表达的GFP分子框架。
GFP分子中,对于肽展示同时保留自体荧光的耐受性存在可变性。因此,现有技术中需要开发可以高水平表达并且耐受插入、同时保留自体荧光的GFP。
除了在末端处支持基因表达的能力以外,GFP可允许将表位插入至分子暴露于介质的表面环中。已进行多次尝试以将多个肽同时插入至GFP的环区域,可允许将蛋白质用于靶特异性结合反应。然而,鉴于GFP及其生色团的结构敏感性,所有这些努力都具有有限的成功。
Pavoor及其同事努力开发了一种经修饰以在两个环结构域中接受外源序列的蛋白。在该开发中,需要几轮的定向进化以选择支持两个近侧区(即Glu-172-Asp-173和Asp-102-Asp-103)中的外源肽的插入的三种突变的蛋白质克隆。作者使用未突变的蛋白质证明两条外源肽的插入阻止酵母细胞表面上的GFP荧光生产和蛋白质表达。在一系列的突变和选择后,在仅两个区域中的同时插入是可能的,但仍导致极大丧失GFP的固有活性,有时使其插入物的生产或表达变为不可能(Pavoor等,PNAS 106(29):11895-11900,2009)。
Abedi等(Nucleic Acids Research 26(2):623-30,1998)提出了环区域中的10个蛋白质位置,其中8个位置在β-折叠之间,用于肽表达。嵌合蛋白可用于需要细胞内表达的实验,因此荧光不受干扰性(uninterruptedness)将是限制因素。在该研究中,仅三种嵌合蛋白(其具有氨基酸157-158、172-173和194-195处的插入位点)显示荧光(减弱为原始的四分之一);和仅两个插入位点(分别地研究)可具有肽而不丧失荧光。文献的作者进一步得出结论“令人好奇的是,即使在β-折叠中的结构扰动GFP是如何如此敏感的”。
Li等(Photochemistry and Photobiology,84(1):111-9,2008)提出了嵌合蛋白(红色荧光蛋白-RFP)的研究,指出在该蛋白质中,六个遗传上不同的位点位于三个不同的环中,在那里可插入五个残基的序列而不干扰蛋白质发荧光的能力。然而,作者并未阐明同时使用这些位点来插入不同的肽。
专利申请WO02090535提出了在蛋白质的5个不同环中非同时插入肽的荧光GFP。该专利申请在其描述性报告中表明同时在蛋白质的多于一个的环中插入肽的可能性,其增加文库的复杂度并允许在同一表面上展示蛋白质。然而,专利文献未证明该可能性,因为其仅提出了在5个不同的蛋白质环中一次一种的肽插入检验。值得注意的是,文献进一步强调了环1和环5其自身并未呈现为良好的插入位点,这是因为在这些位点处的肽插入阻止蛋白质表达。此外,其它专利文献提出了针对蛋白质环中肽表达的GFP变体,然而,这些研究未证明在GFP蛋白质环中不同插入位点中的多于4种肽的同时表达、而不丧失任何其基本特征的可行性(WO02090535、US2003224412、WO200134824)。
发明内容
为了解决上述提及的问题,本发明将提供显著优点,由于容器蛋白可表达大量的不同的多氨基酸序列,特征在于多价容器蛋白,扩展其用于疫苗组合物目的的用途、用于研究和技术开发或疾病诊断的内参。现有技术中仍然存在开发如下容器蛋白的实际需要,所述容器蛋白不仅表现足够的荧光强度,还可在生产细胞系统中大量表达,此外,耐受多条外源多氨基酸序列的伴随展示同时仍表现可检测的自体荧光。
在一方面,本发明涉及能够在容器蛋白上多于4个不同位点处同时展示多条外源多氨基酸序列的蛋白质容器。
在另一方面,本发明涉及能够产生前述蛋白质容器的多核苷酸。
在另一方面,本发明涉及包含前述多核苷酸的载体。
在另一方面,本发明涉及包含前述多核苷酸的表达盒。
在另一方面,本发明涉及用于生产所述蛋白质容器、和用于病原体识别或体外疾病诊断的方法。
在另一方面,本发明涉及所述蛋白质容器用于诊断目的或作为疫苗组合物的用途。
在另一方面,本发明涉及用于诊断目的或作为疫苗组合物的包含所述蛋白质容器的试剂盒。
附图说明
图1–通过亲和层析法的PlatCruzi蛋白的纯化。(A)使用液相层析系统、镍柱上的容器蛋白的洗脱谱。(B)通过收集的13-26洗脱液的聚丙烯酰胺凝胶电泳(SDSPAGE)的分析。由缓冲液B以升序进行洗脱。PM–分子量标记物。
图2–通过ELISA的、PlatCruzi与来自WHO提供的克氏锥虫(Trypanosoma cruzi)国际标准生物参照的血清的反应性。(A)识别TcI株的患者血清的池,称为IS 09/188。(B)识别TcII株的患者血清的池,称为IS09/186。
图3–使用PlatCruzi容器蛋白作为抗原、来自患有慢性恰加斯病的患者的血清的抗体滴度的确定。LACENS提供血清,500ng/孔的浓度和血清稀释度1:50-1:1000用于ELISAS。
图4–针对来自患有不同疾病的患者的血清、通过ELISA的PlatCruzi抗原的表现。以500ng/孔的浓度使用PlatCruzi抗原并以1:250稀释血清。
图5–通过兔抗RxRabies2血清的狂犬病病毒特异性表位的检测。由RxRabies2免疫的兔抗体通过RxRabies2亲和层析法纯化并用作一抗,通过免疫印迹法,以检测粗提取物(*;第2列)或1x和0.5x的两个不同浓度下的半纯化提取物(分别地,第4列和第6列)中的RxRabies2。阴性对照:Rx容器蛋白(第3列)和PlatCruzi(以两个浓度:1x和0.5x分别在第5列和第7列中)。
图6–通过聚丙烯酰胺凝胶电泳(SDS PAGE)的RxHoIgG3蛋白的分析。A,不产生RxHoIgG3的大肠杆菌的可溶性提取物。B,产生RxHoIgG3细菌的水性不溶性部分。C,产生RxHoIgG3细菌的可溶性部分。箭头表示RxHoIgG3蛋白的位置。
图7–通过ELISA的IgM抗RxOro抗体的检测。C-:阴性对照(来自无奥罗普切病毒感染的患者的血清);C+:用于奥罗普切病毒感染的标准阳性血清。患者:奥罗普切病毒感染的疑似病例。Oro+:对于奥罗普切病毒感染为阳性(IgM抗RxOro抗体的检测)。Oro-(阴性对照):无对于RxOro的IgM反应。蛋白质浓度:0.288μg/μL。截断(Cutoff):0.0613。
图8–表示PlatCruzi、RxMayaro_IgG和RxMayaro_IgM蛋白的生产的聚丙烯酰胺凝胶电泳(SDS-PAGE)。第1至8竖列表示:1)分子量;2)无重组蛋白的诱导的总细菌提取物;3)诱导PlatCruzi生产后的总细菌提取物;4)诱导RxMayaro_IgG生产后的总细菌提取物;5)诱导RxMayaro_IgM生产后的总细菌提取物;6)诱导PlatCruzi生产后的不溶性细菌蛋白;7)诱导RxMayaro_IgG生产后的不溶性细菌蛋白;8)诱导RxMayaro_IgM生产后的不溶性细菌蛋白。箭头指出表示PlatCruzi(第3列和第6列)、RxMayaro_IgG(第4列和第7列)和RxMayaro_IgM(第5列和第8列)的条带。
图9–来自马雅罗病毒阳性患者(S MAY)和健康个体(S N)的血清的反应性,通过ELISA,使用RxMayaro_IgG蛋白。由缀合至碱性磷酸酶的抗IgG免疫球蛋白进行显色(截断=0.0210)。
图10–来自被认为健康(S N)和对马雅罗病毒阳性(S MAY)的个体的血清的反应性,通过ELISA,使用RxMayaro_IgM蛋白。由缀合至碱性磷酸酶的抗IgM免疫球蛋白进行显色(截断=0.0547)。
图11–显示来自PlatCruzi、TxCruzi、RxPtx、TxNeuza、和RxYFIgG的不溶性(I)和可溶性(S)蛋白的产量的聚丙烯酰胺凝胶电泳(SDS-PAGE)。第1至10列包括:1)诱导产生PlatCruzi的细菌的不溶性蛋白;2)诱导产生PlatCruzi的细菌的可溶性蛋白;3)诱导产生TxCruzi的细菌的不溶性蛋白;4)诱导产生TxCruzi的细菌的可溶性蛋白;5)诱导产生RxPtx的细菌的不溶性蛋白;6)诱导产生RxPtx的细菌的可溶性蛋白;7)诱导产生TxNeuza的细菌的不溶性蛋白;8)诱导产生TxNeuza的细菌的可溶性蛋白;9)诱导产生RxYFIgG的细菌的不溶性蛋白;10)诱导产生RxYFIgG的细菌的可溶性蛋白。箭头指出表示PlatCruzi(第1列和第2列)、TxCruzi(第3列和第4列)、RxPtx(第5列和第6列)、TxNeuza(第7列和第8列)和RxYFIgG(第9列和第10列)的条带。
图12–具有与来自Covid-19阳性患者血清的IgM抗体反应的SARS-CoV-2的多氨基酸的图案化纤维素膜(Pictorial cellulose membrane),在以棋盘的形式由网格划定的区域中可视化为各种灰色阴影的斑点。各个正方形包括纤维素膜区域的反应斑点,其中以线性形式合成的不同的多肽序列共价结合至膜表面。膜中的物理位置和多氨基酸的序列之间的关系列于表18。组合的多氨基酸序列表示以下的编码序列:刺突蛋白SARS-CoV-2(S1:aa1-1273,A7-K19)、蛋白ORF3a(OF3:aa 1-275,K22-N2)、膜糖蛋白(M:aa1-222,N5-O23);ORF6(OF6:aa 1-61,P2-P12);ORF7蛋白(OF7:aa1-121,P15-Q13)、ORF8蛋白(OF8:aa 1-121,Q16-R17)、核衣壳蛋白(N:aa1-419,R20-V17)、包膜蛋白(E:aa 1-75,W1-W13)、ORF10蛋白区域(OF10:aa1-38,W15-W20)。各个多氨基酸具有15个氨基酸的长度和10个氨基酸的相邻、连续的重叠。
图13–与来自Covid19患者血清的IgG抗体反应的SARS-CoV-2的图案化纤维素多氨基酸膜,在以网格的形式划定的区域中可视化为各种灰色阴影的斑点。各个正方形包括纤维素膜区域的反应斑点,其中以线性形式合成的不同的多肽序列共价结合至膜表面。膜中的物理位置和多氨基酸的序列之间的关系列于表19。组合的多氨基酸序列表示以下的编码序列:SARS-CoV-2ORF3a蛋白(ORF3:aa 1-275,A7-C11)、膜糖蛋白(G:aa 1-61,C14-E8);ORF6蛋白(ORF6:aa 1-61,E11-E21);ORF7蛋白(OF7:aa1-121,E24-F22)、ORF8蛋白(ORF8:aa1-121,G1-G23)、刺突蛋白(S:aa 1-1273,H1-R13)、核衣壳蛋白(N:aa1-419,R16-V1)、包膜蛋白(E:aa 1-75,W1-W13)、ORF10(ORF10:aa 1-38,W15-W20)。各个多氨基酸具有15个氨基酸的长度和10个氨基酸的相邻、连续的重叠。
图14–具有与来自Covid19患者血清的IgA抗体反应的SARS-CoV-2的多氨基酸的图案化纤维素膜,在以网格图案的形式划定的区域中可视化为各种灰色阴影的斑点。各个正方形包括纤维素膜区的反应斑点,其中以线性形式合成的不同的多肽序列共价结合至膜表面。膜中的物理位置和多氨基酸的序列之间的关系列于表20。这些组合的多氨基酸序列表示以下的编码序列:SARS-CoV-2的刺突蛋白(S:aa1-1273,A6-K18)、ORF3a(ORF3:aa1-275,K21-N1)、膜糖蛋白(M:aa 1-61,N4-O22);ORF6(ORF6:aa 1-61,P1-P11);ORF7(ORF7:aa1-121,P14-Q12)、ORF8(ORF8:aa 1-121,Q15-R13)、核衣壳蛋白(N:aa1-419,R16-V1)、包膜蛋白(E:aa 1-75,区域V4-V16)、ORF10(ORF10:aa 1-38,V19-V24)。各个多氨基酸具有15个氨基酸的长度和10个氨基酸的相邻、连续的重叠。
图15–由碱性磷酸酶标记的抗人IgM抗体显色的、来自患有COVID的患者的血清对纤维素膜上合成的SARS-CoV-2肽的反应性(图12)。15A,表面糖蛋白;15B,ORF 3a;15C,膜糖蛋白;15D,ORF 6;15E,ORF 7;15F,ORF 8;15G,核蛋白;15H,E蛋白;15I,ORF 10。
图16–由碱性磷酸酶标记的抗人IgG抗体显色的、来自患有COVID的患者的血清对纤维素膜上合成的SARS-CoV-2肽的反应性(图13)。16A ORF 3a;16B:膜糖蛋白;16C:ORF 6;16D:ORF 7;16E:ORF 8;16F:核蛋白;16G:E蛋白;16H:ORF 10。
图17–由碱性磷酸酶标记的抗人IgG抗体显色的、来自患有COVID的患者的血清对纤维素膜上合成的SARS-CoV-2肽的反应性(图14)。17A,表面糖蛋白;17B,ORF 3a;17C,膜糖蛋白;17D,ORF 6;17E,ORF 7;17F ORF 8;17G,核蛋白;17H,E蛋白;17I,ORF 10。
图18–来自住院患者(n=36)(组3)的血清的ELISA,采用支链合成肽(SARS-X1-SARS-X8),由抗IgM二抗显色。
图19–来自住院患者(n=36)的血清的ELISA,采用支链合成肽(SARS-X1-SARS-X8)、由抗IgG二抗显色。
图20–来自住院患者(n=36)的血清的ELISA,采用支链合成肽(SARS-X4-SARS-X8)、由抗IgA二抗显色。
图21–来自四个患者组(组1:无症状,2:疑似;3:住院,和4:免疫保护)的血清的ELISA,采用SARS-X3支链合成肽、由抗IgM二抗显色。
图22–来自四个患者组(组1:无症状,2:疑似;3:住院,和4:免疫保护)的血清的ELISA,采用SARS-X8支链合成肽、由抗IgG二抗显色。
图23–来自四个患者组(组1:无症状,2:疑似;3:住院,和4:免疫保护)的血清的ELISA,采用合成肽SARS-X7、由抗IgA二抗显色。
图24-对聚丙烯酰胺凝胶(SDS-PAGE)进行电泳表明Ag-Covid19、具有六个组氨酸的尾的Ag-COVID19蛋白、Tx-SARS-IgM、Tx-SARS2-IgG、Tx-SARS2-G/M、Tx-SARS2-IgA、Tx-SARS2-Universal和Tx-SARS2-G5的生产。第1至10竖列,表示:1)分子量;2)无重组蛋白的诱导的总细菌提取物;3)诱导Ag-COVID19生产后的总细菌提取物;4)诱导具有六个组氨酸尾的Ag-COVID19蛋白生产后的总细菌提取物;5)诱导Tx-SARS2-IgM蛋白生产后的总细菌提取物;6)诱导Tx-SARS2-IgG蛋白生产后的总细菌提取物;7)诱导Tx-SARS2-G/M蛋白生产后的总细菌提取物;8)诱导Tx-SARS2-IgA蛋白生产后的总细菌提取物;9)诱导Tx-SARS2-Universal蛋白生产后的总细菌提取物和10)诱导Tx-SARS2-G5蛋白生产后的总细菌提取物。表示分子量标准的字母为A)250kDa;B)130kDa;C)100kDa;D)70kDa;E)55kDa;F)35kDa和G)25kDa。
图25-对聚丙烯酰胺凝胶(SDS-PAGE)进行电泳表明通过亲和层析法的Ag-COVID19蛋白的纯化。(总)诱导生产后的总细菌提取物的谱;(FT)未结合在镍柱上的蛋白质的谱;(200)添加200mM咪唑后的Ag-COVID19蛋白的洗脱谱;(75)添加75mM咪唑后的Ag-COVID19蛋白的洗脱谱和(500)添加500mM咪唑后的Ag-COVID19蛋白的洗脱谱。
图26-对聚丙烯酰胺凝胶(SDS-PAGE)进行电泳表明通过亲和层析法的Tx-SARS2-G5蛋白的纯化。(总)诱导生产后的总细菌提取物的谱;(FT)未结合在镍柱上的蛋白质的谱;(200)添加200mM咪唑后的Tx-SARS2-G5蛋白的洗脱谱;(75)添加75mM咪唑后的Tx-SARS2-G5蛋白的洗脱谱和(500)添加500mM咪唑后的Tx-SARS2-G5蛋白的洗脱谱。
图27–来自感染有疟疾、登革热或SARS-CoV-2并且仍被收治(住院)、康复、疑似或无症状的七组患者的血清的ELISA。作为对照,使用了在流行前收集的来自健康人的血清的集合。Ag-COVID19蛋白用于ELISA并且由抗人IgG二抗显色结合抗体。
图28-来自患有梅毒、疟疾、登革热或者被收治(住院)或疑似的SARS-CoV2的六组患者的血清的ELISA检验。作为对照,使用了在流行前收集的来自健康人的血清的集合。Tx-SARS2-G5蛋白用于ELISA并且由抗人IgG二抗显色结合抗体。
图29–在由Ag-COVID19蛋白免疫小鼠后2周或4周的小鼠中,针对Ag-COVID19、通过ELISA的抗体滴定。
图30–使用Ag-COVID19蛋白的抗体纯化。
具体实施方式
尽管本发明易受到不同实施方案的影响,但优选实施方案示于附图和以下详细讨论中,应理解,本说明书应考虑为本发明的原理的示例并且不旨在限制已在本文中说明和描述的本发明。
在本文中将使用一些缩写。以下为缩写的列表:
关于含氮碱基:
C=胞嘧啶;A=腺嘌呤;T=胸腺嘧啶;G=鸟嘌呤
关于氨基酸:
I=异亮氨酸;L=亮氨酸;V=缬氨酸;F=苯丙氨酸;M=甲硫氨酸;C=半胱氨酸;A=丙氨酸;G=甘氨酸;P=脯氨酸;T=苏氨酸;S=丝氨酸;Y=酪氨酸;W=色氨酸;Q=谷氨酰胺;N=天冬酰胺;H=组氨酸;E=谷氨酸;D=天冬氨酸;K=赖氨酸;R=精氨酸。
蛋白质容器
本发明涉及蛋白质容器的生产和在各种方法和组合物中的使用,所述蛋白质容器基于本文中称为GFP的绿色荧光蛋白的序列,所述方法和组合物利用所述蛋白质容器以在多于四个的不同蛋白质位点处同时展示多条不同或相同的外源多氨基酸序列的能力,和进一步地表现充分的荧光强度的能力、在细胞蛋白生产系统中有效表达的能力、和用作用于研究、诊断、或在疫苗组合物中的试剂的能力。
在第一实施方案中,本发明涉及支持在不同位点处同时插入四条以上的外源多氨基酸序列的稳定蛋白质结构。在另一实施方案中,蛋白质容器包括SEQ ID NO:1中所示的氨基酸序列。在另一实施方案中,蛋白质容器包括SEQ ID NO:3中所示的氨基酸序列。在另一实施方案中,蛋白质容器包括SEQ ID NO:77中所示的氨基酸序列。在另一实施方案中,蛋白质容器在朝向外部环境的蛋白质环中呈现用于外源多氨基酸序列的插入位点。在另一实施方案中,外源多氨基酸序列的同时插入不干扰容器蛋白的生产条件。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列,用于疫苗组合物、用于诊断、或用于实验室试剂的开发。在另一实施方案中,在将外源多氨基酸序列同时插入至容器蛋白的蛋白质环时,外源多氨基酸序列不丧失它们的免疫原性特性。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15和SEQ ID NO:16。在另一实施方案中,蛋白质容器包含SEQ ID NO:.18中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列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和SEQ ID NO:29。在另一实施方案中,蛋白质容器包含SEQ ID NO:20中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ ID NO:30的多个拷贝。在另一实施方案中,蛋白质容器包含SEQ ID NO:31中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39和SEQ ID NO:40。在另一实施方案中,蛋白质容器包含SEQ ID NO:.33中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43和SEQ ID NO:44。在另一实施方案中,蛋白质容器包含SEQ ID NO:45中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49和SEQ ID NO:50。在另一实施方案中,蛋白质容器包含SEQ IDNO:51中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ ID NO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:95和SEQ IDNO:96。在另一实施方案中,蛋白质容器包含SEQ ID NO:64中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ ID NO:65、SEQ ID NO:66、SEQ IDNO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:72、SEQ IDNO:73、SEQ ID NO:74和SEQ ID NO:97。在另一实施方案中,蛋白质容器包含SEQ ID NO:75中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ IDNO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ ID NO:84、SEQ IDNO:85、SEQ ID NO:86、SEQ ID NO:87和SEQ ID NO:98。在另一实施方案中,蛋白质容器包含SEQ ID NO:88中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含外源多氨基酸序列SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ IDNO:15、SEQ ID NO:16、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:94和SEQ ID NO:99。在另一实施方案中,蛋白质容器包含SEQ ID NO:90中所示的氨基酸序列。在另一实施方案中,蛋白质容器同时包含如SEQ ID NO:100、124、125、和126中所限定的外源多氨基酸序列;或者,同时包含如SEQ ID NO:101、127、128、129、130、131、132、133、134、和135中所限定的外源多氨基酸序列;或者,同时包含如SEQ ID NO:136、137、138、139、140、141、142中所限定的外源多氨基酸序列;或者,同时包含如SEQ ID NO:129、133、135、137、140、141、142、143、144、146、147、和148中所限定的外源多氨基酸序列;或者,同时包含如SEQ ID NO:103、149、150、151、152、153、154、155中所限定的外源多氨基酸序列;或者,同时包含如SEQ ID NO:104、156、157、158、159、160、161、162、和163中所限定的外源多氨基酸序列;或者,同时包含如SEQ ID NO:136、139、140、141、142、143、144、146和147中所限定的外源多氨基酸序列。在另一实施方案中,蛋白质容器包含SEQ ID NO:334-341中所示的任意氨基酸序列。
本发明的另一实施方案涉及细胞系统中所述蛋白质容器的有效表达,基于在容器蛋白上10个不同位点处伴随携带一条或两条、或多于两条、三条或四条、或多于十条外源多氨基酸序列的GFP的序列。具体地,本发明涉及在多达10个不同蛋白质位点处同时展示外源多氨基酸序列的所述蛋白质容器的有效表达。更具体地,本发明涉及所述容器的有效表达,其携带插入至10个不同蛋白质位点的所述外源多氨基酸序列,然而不损失其例如自体荧光等固有特性。
本发明还涉及蛋白质容器的生产和使用,“平台”、“Rx”和“Tx”,及它们的氨基酸序列(分别描述于SEQ ID NO:1、SEQ ID NO:3和SEQ ID NO:77),它们的核苷酸序列(分别描述于SEQ ID NO:2、SEQ ID NO:4和SEQ ID NO:78),和包括选择的外源多氨基酸序列的它们的氨基酸序列(描述于SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:31、SEQ ID NO:.33、SEQ IDNO:45、SEQ ID NO:51、SEQ ID NO:64、SEQ ID NO:75、SEQ ID NO:88和SEQ ID NO:90)。通过插入辅助元件(accessory element),还可对容器蛋白进行开发其用途所必需的修饰。还可将有助于纯化过程的序列添加至容器蛋白,例如,但不限于,多组氨酸尾、几丁质结合蛋白、麦芽糖结合蛋白、钙调素结合蛋白、strep-tag、和GST。例如硫氧嘧啶(thiorodixin)等用于稳定的序列也可整合到容器蛋白中。例如V5、Myc、HA、Spot、FLAG序列等可有助于任何抗体检测过程的序列也可添加至容器蛋白。
此外,为了本发明的目的,如通过例如FASTA、BLAST或Gap等公知的序列同一性评价算法所测定的,包括与本文所描述的蛋白和多氨基酸受体为至少约85%、更优选至少约90%、95%、96%、97%、98%或99%同一性的序列。
还可将起到用于蛋白酶的靶切割位点(催化部位)的作用的序列添加至蛋白质容器,允许主蛋白从上述辅助元件分离,包括严格用于优化蛋白质的生产或纯化的目的,但对所建议的最终用途没有贡献。包含起到用于蛋白酶的靶标的作用的位点的这些序列可在任何地方插入,并且包括但不限于,凝血酶、因子Xa、肠肽酶、PreScission、TEV(Kosobokova等,Biochemistry,8:187-200,2015)。而另一种标记蛋白酶的辅助序列(accessorysequence)可为AviTag,其允许在蛋白质表达期间或之后在单点处的特定生物素化。在该情况下,可以通过组合不同的元件来产生标记的蛋白(Wood,Current Opinion inStructural Biology,26:54-61,2014)。
可进一步体外修饰分离的容器蛋白用于不同用途。
多核苷酸
在第一实施方案中,本发明涉及一种多核苷酸,其包含SEQ ID NO:2、4、78、17、19、32、34、46、52、63、76、89、91、326-333任一者和它们的简并序列,能够分别地产生由SEQ IDNO:1、3、77、18、20、31、33、45、51、64、75、88、90、334-341限定的多肽。
本发明还提供了通过任何表达系统从DNA分子产生的分离的容器蛋白,所述DNA分子包括含有编码选择的容器蛋白的核苷酸序列的调控元件。
就一个或多个氨基酸残基的同一性或位置而言,通过氨基酸的缺失、添加、或取代,编码容器蛋白的DNA序列不同于天然存在的GFP的形式的DNA序列。但是,它们仍保留天然存在的形式固有的一些或全部特征,例如但不限于,荧光产生、特征三维形状、在不同系统中表达的能力、和接受外源肽的能力。
编码本发明的容器蛋白的DNA序列包括:整合用于通过某些表达系统的表达的偏好密码子;插入用于限制性酶的切割位点;插入用于促进表达载体构建的优化序列;插入增强子(facilitator)序列以包含待引入容器蛋白的选择的多氨基酸序列。所有这些策略在本领域中为已知的。
此外,本发明进一步提供例如在SEQ ID NO:2、SEQ ID NO:4和SEQ ID NO:78中所描述的序列中添加编码容器蛋白的核苷酸序列的遗传元件。此外,提供了这样的元件,其包含编码容器蛋白的核苷酸序列,所述序列添加编码所选择的外源多氨基酸序列的DNA。此类遗传元件包含描述于SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:32、SEQ ID NO:34、SEQ IDNO:46、SEQ ID NO:52、SEQ ID NO:63、SEQ ID NO:76、SEQ ID NO:89和SEQ ID NO:91中的序列。
容器蛋白表达所需的调控元件包括用于结合至RNA聚合酶的启动子序列和用于结合至核糖体的翻译起始序列。例如,细菌表达载体必须包括适合于细胞系统和翻译起始的起始密码子、启动子、Shine-Dalgarno序列。类似地,真核表达载体包括启动子、起始密码子、下游过程多腺苷酸化信号、和终止密码子。这样的载体可为市售获得的,或从已知的现有技术序列建立的。
载体
在第一实施方案中,本发明涉及包含如上所定义的多核苷酸的载体。
从一个质粒至另一载体的转换可通过添加或删除限制性位点改变核苷酸序列而不修改氨基酸序列来实现,这可通过核酸扩增技术来完成。
表达盒
在第一实施方案中,本发明涉及包含如上所定义的多核苷酸的表达盒。
其它系统中的优化表达可通过改变核苷酸序列以添加或删除限制性位点、并且还优化密码子用于与新表达系统的偏好密码子的比对而不改变最终氨基酸序列来实现。
细胞
在第一实施方案中,本发明涉及包含如上所定义的载体或表达盒的细胞。
本发明进一步提供了含有编码容器蛋白、或添加来自编码所选择的外源多氨基酸序列的DNA的容器蛋白的核苷酸序列的细胞,以起到用于容器蛋白的表达系统的作用。细胞可以是细菌、真菌、酵母、昆虫、植物、或甚至动物细胞。可将编码添加自编码所选择的外源多氨基酸序列的DNA的容器蛋白的DNA序列插入至病毒,所述病毒可用于容器蛋白的表达和生产,作为递送系统,例如杆状病毒、腺病毒、腺病毒相关病毒、甲病毒、疱疹病毒、痘病毒、逆转录病毒、慢病毒,但不限于这些。
有各种将外源遗传物质引入细胞的方法,全部为现有技术中已知的。例如,外源DNA物质可通过磷酸钙沉淀技术而引入至细胞。其它技术可用于本发明的开发,例如使用电穿孔、脂质体转染、显微注射、逆转录病毒载体和诸如腺病毒相关病毒系统等其它病毒载体系统等。
本发明提供包括至少含有DNA分子的细胞的活生物体,所述DNA分子包含用于编码容器蛋白的序列的表达的调控元件。本发明可用于脊椎动物、非脊椎动物、植物和微生物中的容器蛋白的生产。
容器蛋白的表达可在以下中进行,但不限于此:大肠杆菌(Escherichia coli)细胞、枯草芽孢杆菌(Bacillus subtilis)、酿酒酵母(Saccharomyces cerevisiae)、毕赤酵母(Pichia pastoris)、甲醇毕赤酵母(Pichia methanolica)、博伊丁假丝酵母(Candidaboidinii)、安格斯毕赤酵母(Pichia angusta)、哺乳动物细胞如CHO细胞、HEK293细胞或昆虫细胞如Sf9细胞。所有现有技术中已知的原核或真核蛋白表达系统可用于生产容器蛋白。
在本发明的一个开发中,携带用于容器蛋白的编码序列的病毒或噬菌体可感染特定种类的细菌或真核细胞并在该细胞系统中提供容器蛋白的表达。可通过检测容器蛋白的表达来容易地观察到感染。类似地,携带编码容器蛋白的序列的真核植物或动物细胞病毒可感染特定细胞类型并导致容器蛋白在真核细胞系统中的表达。
蛋白质容器的生产方法
在第一实施方案中,本发明涉及生产蛋白质容器的方法,包括将如上定义的多核苷酸引入感兴趣的感受态细胞;进行感受态细胞的培养并进行含有选择的外源多氨基酸的蛋白质容器的分离。在另一实施方案中,蛋白质容器不受到各种外源多氨基酸序列的插入的干扰。
还可通过多种合成生物系统来生产容器蛋白。全合成基因的产生基本上与现有技术中广泛描述的三种基于连接的合成系统相关。
本发明提供使用包括以下的蛋白质表达系统的生产容器蛋白的方法:将用于编码容器蛋白的DNA序列加上用于编码选择的外源多氨基酸序列的DNA引入感兴趣的感受态细胞,在有利于产生含有选择的多氨基酸序列的容器蛋白的条件下培养这些细胞,并分离含有选择的外源多氨基酸的容器蛋白。
本发明进一步提供生产含有选择的外源多氨基酸的容器蛋白的技术。本发明展示用于表达含有选择的外源多氨基酸的容器蛋白的有效方法,其促进感兴趣的蛋白质的大量生产。可在不同细胞系统中进行容器蛋白的生产方法,例如酵母、植物、植物细胞、昆虫细胞、哺乳动物细胞、和转基因动物。可通过将可产生期望的氨基酸序列的密码子优化的核酸序列整合到适用于特定细胞系统的质粒中来使用各个系统。该质粒可包含赋予表达系统许多特性的元件,其包括但不限于,促进保留和复制的序列、可选择的标记物、用于转录的启动子序列、转录的RNA的稳定化序列、核糖体结合位点。
现有技术中已知用于分离表达的蛋白质的方法,并且在该方面,容器蛋白可通过任何技术容易地分离。多组氨酸尾的存在允许在细菌系统中的重组蛋白的表达后,纯化重组蛋白(Hochuli等Bio/Technology 6:1321-25;Bornhorst and Falke,MethodsEnzymology 326:245-54)。
本发明进一步考虑了外源多氨基酸的选择(choice)和挑选(selection)。容器蛋白可以包含来自不同来源的不同多氨基酸序列,范围从包括哺乳动物的脊椎动物、无脊椎动物、植物、微生物、或病毒,以促进它们在不同介质中的表达、展示或使用。可使用不同的多氨基酸序列选择方法,例如通过对抗体或其它结合蛋白的结合亲和性的特定选择、或通过表位作图、或现有技术中已知的其它技术。
多氨基酸序列是5至30个氨基酸的序列,其灵敏地或特异性地表示生物体,用于本申请中所描述的任何目的。多氨基酸序列可表示但不限于,这些实例:(i)线性B细胞表位;(ii)T细胞表位;(iii)中和表位;(iv)对病原体或非病原体来源为特异性的蛋白质区域;(v)邻近通常不是免疫应答的靶标的酶的活性位点的区域。这些表位区域可通过各种方法来识别,包括但不限于:斑点(spot)合成分析、随机肽文库、噬菌体展示、软件分析、使用X射线晶体学数据、表位数据库、或其它现有技术的方法。
将外源多氨基酸序列在如上限定的位点处插入容器蛋白令人惊讶地不破坏或干扰蛋白质的遗传特性。在容器蛋白中已识别用于外源多氨基酸序列的8个引入位点(Kiss等Nucleic Acids Res 34:e132,2006;Pavoor等Proc Natl Acad Sci U S A 106:11895-900,2009;Abedi等,Nucleic Acids Res 26:623-30,1998;Zhong等Biomol Eng 21:67-72,2004)。
这些引入位点可在同一插入位点处串联地(in tandem)包含一个、两个、或更多个不同外源多氨基酸序列,极大地扩大不同多氨基酸序列的表达。
病原体识别或体外疾病诊断的方法
在第一实施方案中,本发明涉及用于病原体识别或体外疾病诊断的方法,其特征在于,所述方法使用如上所定义的容器蛋白。在另一实施方案中,所述方法用于诊断恰加斯病、狂犬病、百日咳、黄热病、奥罗普切病毒病毒感染、马雅罗、IgE超敏反应、屋尘螨(D.pteronyssinus)过敏、或COVID-19。
蛋白质容器的用途
在第一实施方案中,本发明涉及所述蛋白质容器作为实验室试剂的用途。在进一步的实施方案中,本发明涉及所述蛋白质容器用于生产用于针对恰加斯病、狂犬病、百日咳、黄热病、奥罗普切病毒病毒感染、马雅罗、IgE超敏反应、屋尘螨过敏、或COVID-19的免疫的疫苗组合物的用途。
此外,本发明涉及用于使用基于GFP的单一蛋白质容器的、多种多氨基酸序列的伴随表达的系统,用于不同用途,例如作为用于研究的试剂、用于诊断、或用于疫苗组合物。具体地,所述表达系统可起到有用的研究试剂的作用以通过结合表位来纯化抗体。此外,所述表达系统还可起到用于诊断慢性和传染性疾病的免疫学和/或分子学技术的作用。并且,所述表达系统可有利地用于含有用于动物和人的免疫的多种抗原的疫苗组合物。
此外,本发明的一个实施方案是使用基于GFP的单一蛋白质容器的、多种多氨基酸序列的伴随生产的方法,用于不同用途,例如作为用于研究的试剂、用于诊断、或用于疫苗组合物。
本发明进一步展示容器蛋白的某些用途。这些用途包括但不限于,蛋白质容器作为以下的用途:(i)作为细胞筛选检验中的报告分子,包括细胞内检验;(ii)作为用于展示随机或选择的肽文库的蛋白;(iii)作为抗原呈递蛋白,作为用于开发体外免疫学诊断试验的试剂,通常用于传染性、寄生性或其它免疫学疾病;(iv)作为用于选择、捕捉、筛选或纯化例如抗体等结合物质的抗原呈递蛋白;(v)作为用于疫苗组合物的抗原呈递蛋白;(vi)作为含有用于结合抗原的抗体序列的蛋白;(vii)作为具有被动免疫活性的抗原呈递蛋白。
容器蛋白可通过特别地具有以下来用作疫苗组合物:(a)大量的、同时的免疫应答诱导多氨基酸序列,和(b)非免疫应答诱导核心蛋白的。
诊断试剂盒
在第一实施方案,本发明涉及包含如上所定义的蛋白质容器的诊断试剂盒。
最后,通过下文中给出的实施例详细描述本发明。应强调的是,本发明不限于这些实施例,并且其还包括可开发的范围内的变化和修改。还值得注意的是,对巴西遗传遗产(Brazilian genetic heritage)的所有生物序列的授权使用登记在SISGEN,注册号AC53976。
实施例
实施例1-容器蛋白构建
绿色荧光蛋白的不同实例之间的氨基酸序列,eGFP(GenBank:L29345.1;UniProtKB-P42212)、Cycle-3(GenBank:CAH64883.1)、SuperFolder(GenBank:AOH95453.1)、Split(Cabantous等Science Reports 3:2854,2013)、Superfast(Fisher&DeLisa.PLoS One 3:e2351,2008),用于构建本发明的新的蛋白。通过Intaglio软件(Purgatory Design,V3.9.4)进行序列比对和比较。自这些数据,进行某些变化使得容器蛋白可实现所需的特性。
进行改变以产生限制性酶作用位点。设计这些位点的插入,使得可不改变GFP蛋白的物理化学特性,因此不影响本专利申请中所描述的性质或质量。此外,通过允许在基因工程方法和过程中的潜在使用,这些限制性位点的插入将允许这些蛋白的基因操纵,以将各种肽整合到蛋白质的不同区域中,从而向容器蛋白添加进一步的性质。
操纵GFP蛋白的核苷酸序列以引入或替换核苷酸,从而产生新的限制性酶位点。由此,产生两种新的容器蛋白,“平台(Platform)”蛋白和“Rx”蛋白。
基于eGFP蛋白的核苷酸序列中的改变,导致容器蛋白中的以下氨基酸变化:
“平台”蛋白
位置16,氨基酸I;
位置28,氨基酸F;
位置30,氨基酸R;
位置39,氨基酸I;
位置43,氨基酸S;
位置72,氨基酸S;
位置99,氨基酸Y;
位置105,氨基酸T;
位置111,氨基酸E;
位置124,氨基酸V;
位置128,氨基酸I;
位置145,氨基酸F;
位置153,氨基酸T;
位置163,氨基酸A;
位置166,氨基酸T;
位置167,氨基酸V;
位置171,氨基酸V;
位置205,氨基酸T;
位置206,氨基酸I;
位置208,氨基酸L。
“Rx”蛋白
位置16,氨基酸V;
位置28,氨基酸S;
位置30,氨基酸R;
位置39,氨基酸I;
位置43,氨基酸T;
位置72,氨基酸A;
位置99,氨基酸S;
位置105,氨基酸K;
位置111,氨基酸V;
位置124,氨基酸V;
位置128,氨基酸T;
位置145,氨基酸F;
位置153,氨基酸T;
位置163,氨基酸A;
位置166,氨基酸T;
位置167,氨基酸V;
位置171,氨基酸V;
位置205,氨基酸T;
位置206,氨基酸V;
位置208,氨基酸S。
对于所有的容器蛋白,仍可选择以下位置处的可选的氨基酸取代:
位置39,氨基酸N;
位置72,氨基酸S;
位置99,氨基酸S;
位置105,氨基酸Y或K;
位置206,氨基酸I;
位置208,氨基酸L。
一些突变的存在可影响蛋白质的生物化学特性。S30R突变正向地影响蛋白质的螺旋特性;Y145F和I171V突变防止不期望的中间体的翻译;A206V或I突变降低新生蛋白(nascent protein)的聚集的可能性。
对容器蛋白“平台”和“Rx”进行的其它改变,从包含新的核苷酸密码子至产生新的限制性位点,示于表1(下文)。
表1
氨基酸序列变化 | 取代的核苷酸 | 引入的核苷酸 | 要使用的限制性酶 |
D102_D103insV | - | GTC | AatII |
G116_D117insT | - | ACC | KpnI |
L137_G138insK | - | AAG | AfIII |
D191_P192insG | - | GGT | RsrII |
E213_K214insL | - | CTC | SacI |
此外,容器蛋白“平台”和“Rx”的核苷酸序列具有用于NdeI和NheI的两个附加的限制性位点,位于蛋白质的5’氨基末端,来自序列CATATGGTGGCTAGC(SEQ ID NO:5)的插入,和用于EcoRI和XhoI的另两个限制性位点,位于3’羧基末端,来自序列GAATTCTAATGACTCGAG(SEQ ID NO:6)的插入。此外,位于氨基末端的两个终止密码子和多组氨酸尾已整合到容器蛋白中。
“平台”蛋白的氨基酸序列可示于SEQ ID NO:1并且其相应的核苷酸的序列描述于SEQ ID NO:2。
“Rx”蛋白的氨基酸序列可示于SEQ ID NO:3并且其相应的核苷酸的序列描述于SEQ ID NO:4。
通过产生限制性位点而不改变原始蛋白质的三维结构,用于外源多氨基酸序列的10个新的插入位点允许出现在蛋白质中。各个新的插入位点将在本文中称为位置1至位置10。
容器蛋白“平台”和“Rx”的位置1至10在核苷酸和氨基酸序列中的位置示于表2(下文)。
表2
从不同GFP蛋白的氨基酸序列的比对来看,共有氨基酸序列指定为CGP(Dai等Protein Engineering,Design and Selection 20(2):69-79 2007)。尽管表现高稳定性,该荧光蛋白通过定向进化为表现相对于CGP更好的稳定性来得到改进(Kiss等ProteinEngineering,Design&Selection 22(5):313-23,2009)。然而,由于三种突变的存在,增强的蛋白易于聚集。基于其晶体结构的分析,还整合了其它突变,导致聚集的消除和称为热绿色蛋白(Thermal Green Protein)(TGP)的蛋白质的生产(Close等Proteins 83(7):1225-37,2015)。当用作蛋白质容器时,序列称为“Tx”。“Tx”蛋白的氨基酸序列可示于SEQ ID NO:77,并且其对应的核苷酸中的序列描述于SEQ ID NO:78。
“Tx”容器蛋白的位置1至13的核苷酸和氨基酸序列位置示于表3(下文)。在容器蛋白的氨基和羧基末端,两条多氨基酸序列可在两端连续插入。因此,插入位点1a和1b和13a和13b的特征在于其分别在氨基和羧基末端区域。
表3
蛋白质容器中的位置 | 氨基酸序列中的位置 |
1 | GAHASVIKPE |
2 | NG |
3 | YE |
4 | GAPLPFS |
5 | AFPE |
6 | EDQ |
7 | GD |
8 | NFPPNGPVMQKK |
9 | DG |
10 | EGGG |
11 | KKDVRLPDA |
12 | DKDYN |
13 | RYSG |
实施例2–PlatCruzi蛋白的构造
基因工程化“平台”容器蛋白以拥有克氏锥虫表位,本文中我们称其为PlatCruzi平台。对应于PlatCruzi蛋白的基因,本文中称为PlatCruzi基因,描述于核苷酸序列SEQ IDNO:17。
考虑对用于恰加斯病的诊断试验的特异性和灵敏度的实验数据,从可获得的现有技术文献选择源自克氏锥虫的多氨基酸序列(Peralta JM等J Clin Microbiol 32:971-974,1994;Houghton RL等J Infect Dis 179:1226-1234,1999;Thomas等Clin ExpImmunol 123:465-471,2001;Rabello等,1999;Gruber&Zingales,Exp Parasitology,76(1):1-12,1993;Lafaille等,Molecular Biochemistry Parasitology,35(2):127-36,1989)。选择本文中称为TcEp1至TcEp10的10条多氨基酸序列用于插入至“平台”蛋白中的10个插入位点,示于表4(下文)。
在选择克氏锥虫多氨基酸序列后,通过化学合成、通过连接基因合成方法产生对应于PlatCruzi蛋白的合成基因并插入至质粒用于实验。对应于包含表位TcEp1至TcEp10的PlatCruzi基因的氨基酸序列描述于SEQ ID NO:18。
表4
实施例3–PlatCruzi蛋白的开发
通过现有技术的分子生物学技术、使用用于酶NdeI和Xhol的限制性位点将合成基因引入pET28a质粒。为了识别合成基因是否与为PlatCruzi设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化技术、然后测序来分析质粒材料。
使用的测序方法为酶促法、双脱氧法或链终止法,其是基于互补链的酶促合成,互补链的生长通过添加双脱氧核苷酸来停止(Sanger等,Proceeding National Academy ofScience,74(12):5463-5467,1977)。该方法由以下步骤组成:测序反应(热循环仪中25个循环中的DNA复制),通过异丙醇/乙醇的DNA沉淀,双链的变性(95℃,2分钟)和在ABI 3730XL自动测序仪(ThermoFischer SCIENTIFIC)中进行的核苷酸序列的阅读(Otto等,.Geneticsand Molecular Research 7:861-871,2008)。借助于4Peaks程序(Nucleobytes;Mac OS X,2004)完成所获得的序列的分析。来自pET-28a载体(T7启动子和T7终止子)的引物用于反应。
将分析的具有PlatCruzi的正确序列的质粒克隆转移至大肠杆菌菌株BL21以产生PlatCruzi蛋白。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。将菌株在LB培养基中生长过夜,然后再接种在添加有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于尿素缓冲液(100mM NaH2PO4、10mM Tris-base、8M尿素,pH 8.0)中。将溶液经HisTrapTM亲和性柱,1mL,GE Healthcare Life Sciences,进行层析,这允许组氨酸标记的蛋白的高分辨率纯化。以0.5mL每分钟的流动速率将上清液施加至镍亲和性柱(HisTrapTM,1mL,GE Healthcare Life Sciences),所述柱先前在缓冲液A(50mM Tris-HCl,pH 8.0、100mM NaCl和5mM咪唑)中平衡。结合后,用10mL的缓冲液A洗涤树脂。以0.7mL/分钟的流动速率在100%梯度的缓冲液B(50mM Tris-HCl,pH 8.0、100mM NaCl和500mM咪唑)中洗脱蛋白45分钟。然后在280nm处对PlatCruzi纯化(黑线)并示于图1A。咪唑的百分比标记为红色。在约19至25ml的体积中洗脱蛋白。
对重组蛋白的试样(1μg/孔)进行含有SDS的聚丙烯酰胺凝胶电泳(SDS-PAGE)(Laemmli,Nature 227:680-685,1970)。分别在4%和11%的丙烯酰胺浓度下制备浓缩凝胶(浓缩胶(stacking gel))和分离凝胶(分离胶(running gel))(表5,下文)。在变性条件下,在62.5mM Tris-HCl缓冲液、pH 6.8、2%SDS、5%β-巯基乙醇、10%甘油中制备样品,并在95℃下煮5分钟(Hames BD,Gel electrophoresis of proteins:a practicalapproach.3.ed.Oxford.1998)。电泳后,通过用考马斯亮蓝(comassie blue)R250(Bio-Rad,USA)染色来检测蛋白。KaleidoscopeTM Prestained Standards标记物用作分子量参照(Bio-Rad,USA)。图1B,显示使用液相层析系统、使用镍-琼脂柱、通过亲和层析法的PlatCruzi蛋白的纯化。
表5:用于制备4%样品浓缩胶和用于11%分离胶的试剂的体积和浓度
实施例4–自PlatCruzi的ELISA的开发
针对一组参照生物样品和由克氏锥虫感染的个体评价PlatCruzi蛋白的表现。将在碳酸盐/碳酸氢盐缓冲液(50mM,pH 9.6)中的PlatCruzi蛋白以0.1、0.25、0.5和1.0μg/孔的量添加至96孔ELISA板中,在4℃下12-18小时。用添加有Tween 20(PBS-T,10mM磷酸钠-Na3PO4,150mM氯化钠–NaCl和0.05%Tween-20,pH 7.4)的盐水-磷酸盐缓冲液(PBS)溶液洗涤孔,然后在37℃下用含有5%(重量/体积)脱水脱脂乳的1x PBS缓冲液孵育2小时。
然后用PBS-T缓冲液洗涤孔3次,并在37℃下用2、4、8、16、32和64倍稀释的参照生物样品TCl(IS 09/188)或TCII(IS 09/186)(世界卫生组织(World HealthOrganization))孵育1小时。在孵育后,用PBS-T洗涤孔3次,并在37℃下、用以1:5000稀释的碱性磷酸酶标记的人IgG抗体孵育1小时。再次用PBS-T洗涤3次并添加底物对硝基苯基磷酸盐(PNPP,1mg/mL,ThermoFischer SCIENTIFIC)。避光下30分钟后,在ELISA读板机中测定405nm下的吸光度。
无论PlatCruzi的使用量,结果显示使用的TCI和TCII参照生物样品的全部稀释度中的令人满意的反应(图2A和2B)。结果强烈支持PlatCruzi用于识别由六种DTU(离散分型单元(discrete typing unit)或不同分型单元)中任一种导致的克氏锥虫感染的用途,覆盖完整地理范围(geographic range)的流行(circulating)克氏锥虫株。当使用来自具有低或高抗体检测滴度的恰加斯病患者的血清时,可观察到相同的表现(图3)。
如上所述制备含有500ng的PlatCruzi(在0.3M尿素中,pH 8.0)的Elisa板,用PBS-T洗涤3次后,以1:50、1:100、1:250、1:500、1:1000的不同稀释度,采用来自具有高抗克氏锥虫抗体指数的四名患者(6C-CE、9C-CE、15C-CE和12-SE)和来自具有低抗克氏锥虫抗体指数的四名患者(3C-PB、6C-PB、16C-PB、和17C-PB)的血清,在37℃下孵育所述Elisa板1小时。此后,用PBS-T洗涤孔3次,并用以1:5000稀释的碱性磷酸酶标记的人IgG抗体孵育1小时。再次用PBS-T缓冲液洗涤孔3次,并添加底物对硝基苯基磷酸盐(PNPP,1mg/mL,ThermoFischerSCIENTIFIC)。30分钟后,在ELISA读板机中测定405nm下的吸光度。
结果显示,对于具有低抗体滴度的血清,1:50、1:100和1:250稀释度下的阅读信号明确地高于由阴性对照达到的阈值,表明PlatCruzi平台用于检测高和低抗体患者血清二者中的抗克氏锥虫抗体的潜力。
用于实验目的的患者血清样品的使用由Fiocruz的伦理委员会(EthicsCommittee of Fiocruz)批准,依据授权书CEP/IOC-CAAE:52892216.8.0000.5248。
实施例5–PlatCruzi ELISA的灵敏度和特异性
采用来自诊断为克氏锥虫的患者的71份血清、加上来自诊断为利什曼病(leishmaniasis)(对于克氏锥虫为阴性)的患者的18份血清、诊断为登革热(对于克氏锥虫为阴性)的患者的20份血清、和39份阴性血清(其它传染病和未感染的个体),以1:250的稀释度,在37℃下孵育Elisa板1小时,所述Elisa板为在上述实施例中开发的含有500ng的PlatCruzi(0.3M尿素,pH 8.0)的Elisa板。其后,对板进行洗涤和抗体标记,如上所述进行显色和阅读过程。
来自接受者操作特征(receiver operating characteristic,ROC)曲线相关分析,结果指出使用PlatCruzi平台的优异灵敏度和特异性(图4)。对于先前识别为对克氏锥虫为阳性的血清,未观察到假阴性结果;以及对于已知对克氏锥虫为阴性的其它血清,包括对于其它传染性疾病为阳性的血清,未观察到假阳性。灵敏度和特异性指数二者皆为100%。
实施例6–RxRabies2蛋白的开发
对“Rx”蛋白测试其表达来自其它微生物、包括病毒的表位的性能和能力。文献指出大量的特定多氨基酸序列可用作用于中和抗体的靶标。然而,病毒株之间观察到的序列中的小的变化可干扰中和。因此,彻底研究最佳使用的多氨基酸序列需要大量的病毒的生物学以及其与其宿主的相互作用的流行病学的知识。
考虑到对用于诊断由狂犬病病毒导致的疾病的特异性和灵敏度的实验数据,从可获得的现有技术文献选择狂犬病病毒多氨基酸序列(Kuzmina等,J Antivir Antiretrovir5:2:37-43,2013;Cai等,Microbes Infect 12:948-955,2010)。
选择本文中称为RaEp1至RaEp10的10条多氨基酸序列用于插入至Rx蛋白中的10个插入位点,如下所述。这些多氨基酸序列与Rx蛋白的序列的组合产生RxRabies2蛋白。对应于RxRabies2蛋白的基因,本文中称为RxRabies2基因,描述于核苷酸序列SEQ ID NO:19。对应于包含多氨基酸序列RaEp1至RaEp10的RxRabies2基因的氨基酸序列描述于SEQ ID NO:20。
表6
多氨基酸序列 | 蛋白质中的位置 | 原始表位蛋白 | 序列 | SEQ ID no. |
RaEp 1 | 1 | 抗原位点1 | CKLKLCGVLGL | SEQ ID no.21 |
RaEp 2 | 2 | 抗原位点1 | CKLKLCGCSGL | SEQ ID no.22 |
RaEp 3 | 3 | 抗原位点1 | CKLKLCGVPGL | SEQ ID no.23 |
RaEp 4 | 4 | - | VDERGLYK | SEQ ID no.24 |
RaEp 5 | 5 | - | WVAMQTSN | SEQ ID no.25 |
RaEp 6 | 6 | 抗原位点III | KSVRTWNEI | SEQ ID no.26 |
RaEp 8 | 8 | g5抗原位点 | LHDFHSD | SEQ ID no.27 |
RaEp 9 | 9 | g5抗原位点 | LHDFRSD | SEQ ID no.28 |
RaEp 10 | 10 | g5抗原位点 | LHDLHSD | SEQ ID no.29 |
已合成包含编码Rx蛋白的序列和上表6中所述的编码多氨基酸序列的序列的合成基因。
通过现有技术分子生物学技术、使用用于酶NdeI和Xhol的限制性位点将合成基因引入pET28a质粒。为了识别合成基因是否与为RxRabies2设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化技术、然后测序技术来分析质粒材料,以与PlatCruzi中所描述的相同的方法进行。
将分析的具有RxRabies2的正确序列的质粒克隆转移至大肠杆菌菌株BL21以产生RxRabies2蛋白。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在LB培养基中生长过夜,然后再接种在具有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并在37℃下维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于尿素缓冲液(100mM NaH2PO4、10mM Tris-base、8M尿素,pH 8.0)中。以0.5mL每分钟的流动速率,将溶液经HisTrapTM亲和性柱,1mL,GEHealthcare Life Sciences,进行层析,这允许组氨酸标记的蛋白的高分辨率纯化,所述柱先前在缓冲液A(50mM Tris-HCl,pH 8.0、100mM NaCl和5mM咪唑)中平衡。结合后,用10mL的缓冲液A洗涤树脂。以0.7mL/分钟的流动速率在100%梯度的缓冲液B(50mM Tris-HCl,pH8.0、100mM NaCl和500mM咪唑)中洗脱蛋白45分钟。
在三种不同培养物体积:3、25和50ml中分析RxRabies2生产。如表7(下文中)中所示,RxRabies2的表达为平均123μg/ml。
表7
实施例7–RxRabies2蛋白作为疫苗组合物
如上述实施例中所描述的产生RxRabies2蛋白。将100μg的蛋白悬浮于弗氏不完全佐剂(Freud’s incomplete adjuvant)(0.5mL)并肌内接种至两只6月龄雄性新西兰兔的四头肌(quadricep)。在初始接种后7天和14天,用悬浮于PBS中的Rx狂犬病蛋白(100μg/0.5mL)再接种兔。
在接种第一剂的疫苗组合物21天后,从动物收集血液。通过离心收集血浆并通过结合吸附至硝化纤维素膜的Rx-Rabies2蛋白来进行亲和性纯化。
如下文中所述制备含有Rx-Rabies2蛋白的硝化纤维素膜以从潜在污染物分离Rx-Rabies2蛋白。电泳后,使用现有技术免疫印迹技术将蛋白质转移至硝化纤维素膜。
11%SDS-PAGE凝胶的制备,如上述实施例和表5中所述;
将10μg的Rx-Rabies2蛋白施加至11%SDS-PAGE凝胶(表5)并使其经受100伏特的电泳电流约2小时;
蛋白质至硝化纤维素膜的转移:使用具有转移缓冲液(25mM Tris base、192mM甘氨酸和20%甲醇)的Trans-Blot Cell(Bio-Rad,USA),在100V下1小时,将蛋白质转移至硝化纤维素膜;
用Ponceau S red(Ponceau S 0.1%,乙酸5%)染色以确认重组蛋白的存在。
剪切膜以使得特别地获得仅具有RxRabies2蛋白的一块;
然后使膜在蒸馏水中脱色并置于TBS(0.1%)中12至18小时(过夜);
用封闭液(含有0.05%(v/v)Tween 20(TBS-T)和5%(w/v)脱脂奶粉的25mM Tris-HCl、125mM NaCl pH 7.4(TBS))孵育过夜,然后再次在封闭液中孵育膜1小时,然后用TBS-T洗涤3次每次5分钟,并用TBS再进行3次洗涤每次5分钟。
将来自免疫的兔的血清在TBS中以1:500稀释,然后在搅拌下、将10ml置于与含有RxRabies2蛋白的硝化纤维素膜片段接触1小时,然后用TBS-T洗涤3次每次5分钟,并再次用TBS洗涤3次每次5分钟。然后,通过添加1ml的100mM甘氨酸(pH 3.0)来释放特异性结合的抗体。通过添加100μl的1M Tris(pH 9.0)将溶液的pH升高至7以纯化兔抗体。特异性结合抗原的抗体的纯化在使用这些抗体用于疗法中是重要步骤,因为其允许显著降低待施用的量同时最小化潜在的不良反应。
不同的提取物用于表明产生的兔抗体结合RxRabies2的特异性能力。使用以下:
具有Rx蛋白表达的细菌粗提取物,使用如PlatCruzi中所提及的相同条件获得;
细菌粗提取物中的RxRAbies2蛋白,并以1x和0.5x浓度纯化;
1x和0.5x浓度下的纯化的PlatCruzi蛋白。
如上所述,对潜在配体进行聚丙烯酰胺凝胶电泳(11%SDS-PAGE,表5),然后转移至硝化纤维素膜并进行免疫印迹法,其细节已针对RxRabies2进行了描述。
在搅拌下,用如上所述的纯化的抗RxRabies2血清孵育膜1小时。然后,用TBS-T洗涤3次每次5分钟,再用TBS洗涤3次每次5分钟。其后,用以1:10,000稀释的过氧化物酶与抗兔IgG二抗孵育膜1小时。在用二抗孵育后,进行用TBS-T洗涤3次每次5分钟和用TBS洗涤3次每次5分钟。借助于SigmaFastTM DAB Peroxidase Substrate Tablet进行显色。
结果显示通过接种RxRabies2产生的兔抗体与含有狂犬病病毒2蛋白的配体的特异性结合。图5显示仅在泳道(lane)2、4、和6中读取条带,其含有RxRabies2蛋白的细菌粗提取物,以及分别为1x浓度和0.5x浓度的纯化和稀释的RxRabies2蛋白。
还可通过泳道3、5和7中的条带的缺失而观察到免疫应答的特异性,包含(i)无表位引入的Rx容器蛋白、(ii)分别地1x和0.5x稀释的Platcruzi平台。这些结果确证免疫应答限于狂犬病病毒表位,表明Rx蛋白自身不是免疫原性的。
实施例8–RxHolgG3蛋白的开发
从马免疫球蛋白的多氨基酸序列的作图研究(De-Simone等,Toxicon 78:83-93,2014;Wagner等,Journal of Immunology 173:3230-3242,2004),鉴定了通过人IgG和IgE识别的马IgG3多氨基酸的序列,其适用于实验室检验以诊断马血清过敏。
将多氨基酸序列DVLFTWYVDGTEV(SEQ ID NO:30)在位置1、5、6、8、9和10处整合到Rx蛋白中,产生RxHolgG3蛋白。RxHolgG3蛋白的氨基酸序列描述于SEQ ID NO:31。RxHolgG3蛋白的核苷酸序列描述于SEQ ID NO:32。合成包含编码Rx蛋白的序列和编码如上所述的多氨基酸序列(SEQ ID NO:30)的序列的合成基因。
通过现有技术分子生物学技术、使用用于酶NdeI和Xhol的限制性位点将合成基因引入pET28a质粒。为了识别合成基因是否与为RxHoIgG3蛋白设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化技术、然后测序来分析质粒材料,已在PlatCruzi中详细描述。
将分析的具有RxHoIgG3的正确序列的质粒克隆转移至大肠杆菌菌株BL21以产生RxHoIgG3蛋白。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在LB培养基中生长过夜,然后再接种在具有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于尿素缓冲液(100mM NaH2PO4、10mM Tris-base、8M尿素,pH 8.0)中。使用镍亲和性柱(HisTrapTM,1mL,GE Healthcare Life Sciences)并以0.5mL每分钟流动,对溶液进行层析,所述柱先前在缓冲液A(50mM Tris-HCl,pH 8.0、100mM NaCl和5mM咪唑)中平衡。结合后,用10mL的缓冲液A洗涤树脂。以0.7mL/分钟的流动速率在100%梯度的缓冲液B(50mM Tris-HCl,pH 8.0、100mM NaCl和500mM咪唑)中洗脱蛋白45分钟。可在11%SDS-PAGE电泳(表5)后的洗脱液中证明RxHolgG3蛋白的生产。结果示于图6,并且显示RxHolgG3作为重组蛋白的表达。在未诱导的可溶性细菌提取物(图6,第1列)未检测到条带,以及在不溶性(第2列)和可溶性(第3列)部分中各自检测到条带。
实施例9–RxOro蛋白的开发
从奥罗普切病毒(oropouche virus)(株Q71MJ4和Q9J945,Uniprot)的多氨基酸序列作图研究(Acrani等,Journal of General Virology 96:513–523,2014Tilston-Lunel等,Journal of General Virology 96(Pt 7):1636–1650,2015),考虑到它们的诊断潜力,我们从现有技术中可获得的斑点合成或肽微阵列技术选择多氨基酸序列。选择本文中称为OrEp1至OrEp7的六条多氨基酸序列用于插入至Rx蛋白中的9个插入位点,如下表8中所示:
表8
上述这些多氨基酸序列与Rx蛋白的组合产生RxOro蛋白。对应于包含多氨基酸序列OrEp1至OrEp6的RxOro基因的氨基酸序列描述于SEQ ID no.33。对应于RxOro蛋白的基因,本文中称为RxOro基因,描述于核苷酸序列SEQ ID no.34。
通过现有技术分子生物学技术、使用用于酶NdeI和Xhol的限制性位点将合成RxOro基因引入pET28a质粒。为了识别合成基因是否与为RxOro设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化和其后的测序技术来分析质粒材料,如PlatCruzi中所述。
将分析的具有RxOro蛋白的正确序列的质粒转移至大肠杆菌菌株BL21。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在LB培养基中生长过夜,然后再接种在具有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于尿素缓冲液(100mM NaH2PO4、10mM Tris-base、8M尿素,pH 8.0)中。使用镍亲和性柱(HisTrapTM,1mL,GE Healthcare Life Sciences)并以0.5mL每分钟流动,对溶液进行层析,所述柱先前在缓冲液A(50mM Tris-HCl,pH 8.0、100mM NaCl和5mM咪唑)中平衡。结合后,用10mL的缓冲液A洗涤树脂。以0.7mL/分钟的流动速率在100%梯度的缓冲液B(50mM Tris-HCl,pH 8.0、100mM NaCl和500mM咪唑)中洗脱蛋白45分钟。以三种不同的细菌生长体积检验RxOro生产:3、25和50ml。RxOro的表达水平为平均203μg/ml,结果示于表9。
表9
实施例10–来自RxOro的ELISA的开发
自针对一组由奥罗普切病毒感染影响的个体的血清评价RxOro蛋白的性能。将在溶液(0.3M尿素,pH 8.0)中的RxOro蛋白以500ng/孔的量添加至96孔ELISA板,在4℃下12-18小时。用添加有Tween 20的盐水-磷酸盐缓冲液(PBS)(PBS-T,10mM磷酸钠-Na3PO4,150mM氯化钠–NaCl和0.05%Tween-20,pH 7.4)洗涤孔,然后在37℃下用含有5%(重量/体积)脱脂奶粉的1x PBS缓冲液孵育2小时。
然后,用PBS-T缓冲液洗涤孔3次,并在37℃下、用1:100稀释的来自疑似奥罗普切病毒感染的患者的98份血清样品和来自健康患者的51份血清样品孵育1小时。孵育后,用PBS-T洗涤孔3次,然后在37℃下、用以1:5000稀释的碱性磷酸酶标记的人IgG抗体孵育1小时。再次用PBS-T缓冲液洗涤孔3次并添加对硝基苯基磷酸盐(PNPP,1mg/mL,ThermoFischerSCIENTIFIC)。避光下30分钟后,在ELISA读板机中测定405nm下的吸光度。
结果指出使用RxOro的优异灵敏度和特异性(图7)。结果强烈支持RxOro用于奥罗普切病毒病毒感染的检测的用途。
用于实验目的的患者血清样品的使用由Fiocruz的伦理委员会批准,依据授权书CEP/IOC-CAAE:52892216.8.0000.5248。
实施例11-RxMayaro_IgG蛋白的开发
从马雅罗病毒(株Q8QZ73和Q8QZ72,Uniprot)的多氨基酸序列作图研究(Espósito等,Genome Announcement 3:e01372-15,2015),考虑到它们的诊断潜力,我们从可获得的现有技术文献选择多氨基酸序列。选择本文中称为MGEp1至MGEp4的四条多氨基酸序列用于插入至Rx蛋白中的9个插入位点,如下表10中所示:
表10
多氨基酸序列 | 蛋白质中的位置 | 原始表位蛋白 | 序列 | SEQ ID no. |
MGEp 1 | 1 | nsP2 | KLSATDWSAI | SEQ ID no.41 |
MGEp 2 | 3 | Capsid | KPKPQPEK | SEQ ID no.42 |
MGEp 3 | 4 | nsP1 | KKMTPSDQI | SEQ ID no.43 |
MGEp 4 | 5 | nsP3 | VELPWPLETI | SEQ ID no.44 |
MGEp 2 | 6 | Capsid | KPKPQPEK | SEQ ID no.42 |
MGEp 1 | 7 | nsP2 | KLSATDWSAI | SEQ ID no.41 |
MGEp 4 | 8 | nsP3 | VELPWPLETI | SEQ ID no.44 |
MGEp 3 | 9 | nsP1 | KKMTPSDQI | SEQ ID no.43 |
MGEp 1 | 10 | nsP2 | KLSATDWSAI | SEQ ID no.41 |
上述这些多氨基酸序列与Rx蛋白的序列的组合产生RxMayaro_IgG蛋白。对应于包含多氨基酸序列MGEp1至MGEp4的RxMayaro_IgG基因的氨基酸序列描述于SEQ ID no.45。对应于RxMayaro_IgG蛋白的基因,本文中称为RxMayaro_IgG基因,描述于核苷酸序列SEQ IDno.46。
通过现有技术已知的分子生物学技术、使用用于酶NdeI和Xhol的限制性位点将合成RxMayaro_IgG基因引入pET28a质粒。为了识别合成基因是否与为RxMayaro_IgG设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化技术、然后测序来分析质粒材料,如PlatCruzi中所引用。
将分析的具有RxMayaro_IgG蛋白的正确序列的质粒转移至大肠杆菌菌株BL21。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在LB培养基中生长过夜,然后再接种在具有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于尿素缓冲液(100mM NaH2PO4、10mM Tris-base、8M尿素,pH 8.0)中。以0.5mL每分钟的流动速率在镍亲和性柱(HisTrapTM,1mL,GEHealthcare Life Sciences)上对溶液进行层析,所述柱先前在缓冲液A(50mM Tris-HCl,pH 8.0、100mM NaCl和5mM咪唑)中平衡。结合后,用10mL的缓冲液A洗涤树脂。以0.7mL/分钟的流动速率在100%梯度的缓冲液B(50mM Tris-HCl,pH 8.0、100mM NaCl和500mM咪唑)中洗脱蛋白45分钟。可在来自进行11%SDS-PAGE电泳(表5)的洗脱液中证实RxMayaro_IgG蛋白的生产。还通过SDS-PAGE检验RxMayaro_IgG蛋白以确证其生产并确定其在可溶性和不溶性部分之间的分布。如图8中所示,第4列和第7列(箭头)显示RxMayaro_IgG作为可溶性和不可溶性产生。
以3种不同生长体积检验RxMayaro_IgG生产:3、25和50ml。如表11(下文)中所示,RxMayaro_IgG的表达水平为平均130μg/ml。
表11
实施例12–来自RxMayaro_IgG的ELISA的开发
针对一组来自由Mayaro病毒感染影响的个体的血清评价RxMayaro_IgG蛋白的性能。将在溶液(0.3M尿素,pH 8.0)中的RxMayaro_IgG蛋白以500ng/孔的量添加至96孔ELISA板,在4℃下12-18小时。用添加有Tween 20的盐水-磷酸盐缓冲液(PBS)(PBS-T,10mM磷酸钠-Na3PO4,150mM氯化钠–NaCl和0.05%Tween-20,pH 7.4)洗涤孔,然后在37℃下用含有5%(重量/体积)脱脂奶粉的1x PBS缓冲液孵育2小时。
然后,用PBS-T缓冲液洗涤孔,并在37℃下、用1:100稀释的来自疑似马雅罗病毒感染的患者的血清的6份样品和来自健康患者的血清的29份样品孵育1小时。孵育后,用PBS-T洗涤孔3次,然后在37℃下、用以1:5000稀释的碱性磷酸酶标记的人IgG抗体孵育1小时。再次用PBS-T缓冲液洗涤孔3次并添加对硝基苯基磷酸盐(PNPP,1mg/mL,ThermoFischerSCIENTIFIC)。避光下30分钟后,在ELISA读板机中测定405nm下的吸光度。
结果指出使用RxMayaro_IgG的优异灵敏度和特异性(图9)。结果强烈支持RxMayaro_IgG用于马雅罗病毒感染的检测的用途。
用于实验目的的患者血清样品的使用由Fiocruz的伦理委员会批准,依据授权书CEP/IOC-CAAE:52892216.8.0000.5248。
实施例13-RxMayaro_IgM蛋白的开发
从马雅罗病毒(株Q8QZ73和Q8QZ72,Uniprot)的多氨基酸序列的作图研究(Espósito等,Genome Announcement 3:e01372-15,2015),考虑到它们的诊断潜力,我们从可获得的现有技术文献选择多氨基酸序列。选择本文中称为MMEp1至MMEp4的四条多氨基酸序列用于插入至Rx蛋白中的9个插入位点,如表12(下文)中所示:
表12
上述这些多氨基酸序列与Rx蛋白的序列的组合产生RxMayaro_IgM蛋白。对应于包含多氨基酸序列MMEp1至MMEp4的RxMayaro_IgM基因的氨基酸序列描述于SEQ ID no.51。对应于RxMayaro_IgM蛋白的基因,本文中称为RxMayaro_IgM基因,描述于核苷酸序列SEQ IDno.52。
通过现有技术已知的分子生物学技术、使用用于酶NdeI和Xhol的限制性位点将合成RxMayaro_IgM基因引入pET28a质粒。为了识别合成基因是否与为RxMayaro_IgM设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化技术、然后测序来分析质粒材料,如在PlatCruzi中先前所描述的。
将分析的具有RxMayaro_IgM蛋白的正确序列的质粒转移至大肠杆菌菌株BL21。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在LB培养基中生长过夜,然后再接种在添加有卡那霉素(30μg/ml)相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于尿素缓冲液(100mM NaH2PO4、10mM Tris-base、8M尿素,pH 8.0)中。以0.5mL每分钟的流动速率在镍亲和性柱(HisTrapTM,1mL,GEHealthcare Life Sciences)上对溶液进行层析,所述柱先前在缓冲液A(50mM Tris-HCl,pH 8.0、100mM NaCl和5mM咪唑)中平衡。结合后,用10mL的缓冲液A洗涤树脂。以0.7mL/分钟的流动速率在100%梯度的缓冲液B(50mM Tris-HCl,pH 8.0、100mM NaCl和500mM咪唑)中洗脱蛋白45分钟。
可通过进行SDS-PAGE电泳在洗脱液中证明RxMayaro_IgM蛋白的生产,并且可观察到其在可溶性和不溶性部分之间的分布。如图8中所示,第5列和第8列(箭头)显示RxMayaro_IgM作为可溶性和不溶性产生。
还以三种不同生长体积检验RxMayaro_IgM生产:3、25和50ml。如表13(下文)中所示,RxMayaro_IgM的表达水平为平均205μg/ml。
表13
实施例14–基于RxMayaro_IgM的ELISA的开发
针对一组来自由马雅罗病毒感染影响的个体的血清评价RxMayaro_IgM蛋白的性能。将在溶液(0.3M尿素,pH 8.0)中的RxMayaro_IgM蛋白以500ng/孔的量添加至96孔ELISA板,在4℃下12-18小时。用添加Tween 20的盐水-磷酸盐缓冲液(PBS)(PBS-T,10mM磷酸钠-Na3PO4,150mM氯化钠–NaCl和0.05%Tween-20,pH 7.4)洗涤孔,然后在37℃下用含有5%(重量/体积)脱脂奶粉的1x PBS缓冲液孵育2小时。
然后,用PBS-T缓冲液洗涤孔3次,并在37℃下、用1:100稀释的来自疑似马雅罗病毒感染的患者的6份血清样品和来自健康患者的29份血清样品孵育1小时。孵育后,用PBS-T洗涤孔3次,然后在37℃下、用以1:5000稀释的碱性磷酸酶标记的人IgM抗体孵育1小时。再次用PBS-T缓冲液洗涤孔3次并添加对硝基苯基磷酸盐(PNPP,1mg/mL,ThermoFischerSCIENTIFIC)。避光下30分钟后,在ELISA读板机中测定405nm下的吸光度。
结果指出使用RxMayaro_IgM的优异灵敏度和特异性(图10)。结果强烈支持RxMayaro_IgM用于马雅罗病毒感染的检测的用途。
用于实验目的的患者血清样品的使用由Fiocruz的伦理委员会批准,依据授权书CEP/IOC-CAAE:52892216.8.0000.5248。
实施例15–蛋白质RxPtx开发
从导致百日咳的细菌毒素蛋白百日咳鲍特氏菌(Bordetella pertussis)(P04977;P04978;P04979;P0A3R5和P04981:Uniprot)的多氨基酸序列的作图研究,考虑到它们的诊断潜力,从可获得的现有技术文献选择多氨基酸序列。选择本文中称为PtxEp1至PtxEp10的10条多氨基酸序列用于插入至Rx蛋白中的9个插入位点,如下表14中所示。在本实施例中,在两个表位中使用间隔区(SEQ ID NO:95:SYWKGS)而将所述两个表位置于位置1处。还使用另一间隔区(SEQ ID NO:96:EAAKEAAK)而将两个表位插入位置10处。引入这些间隔区的目的在于在连续的多氨基酸之间产生惰性物理空间(inert physical space),因此有助于防止邻近抗体之间的结合竞争。
表14
上述这些多氨基酸序列与Rx蛋白的序列组合产生蛋白RxPtx。对应于包含表位PtxEp1至PtxEp10的RxPtx基因的氨基酸序列描述于SEQ ID no.64。对应于RxPtx蛋白的基因,本文中称为RxPtx基因,描述于核苷酸序列SEQ ID no.63。
通过现有技术分子生物学方法、使用用于酶NdeI和Xhol的限制性位点将合成基因RxPtx引入pET28a质粒。为了识别合成基因是否与为RxPtx设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化和其后的测序技术来分析质粒材料,如在PlatCruzi中先前所描述的。
将分析的具有RxPtx蛋白的正确序列的质粒转移至大肠杆菌菌株BL21。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在LB培养基中生长过夜,然后再接种在添加有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于2mL的具有CelLytic(0.5x)的PBS中,在4℃下1小时。在另一次离心后,收集上清液并将沉淀重悬于与上清液相同体积的8M尿素溶液(pH8.0)中。将相等的体积上样至SDS-PAGE凝胶(11%,表5)。
通过SDS-PAGE电泳检验RxPtx蛋白以证明其生产并确定其在可溶性和不溶性部分之间的分布。如图11中所示,第5列和第6列(箭头)显示RxPtx作为可溶性和不溶性产生,在不溶性部分中具有更高比例。
实施例16–RxYFIgG蛋白的开发
从黄热病病毒(p03314-Uniprot档案中的株17DD和序列)的多氨基酸序列的作图研究,考虑到它们的诊断潜力,从可获得的现有技术文献选择多氨基酸序列。选择本文中称为YFIgGEp1至YFIgGEp10的10条多氨基酸序列用于插入至Rx蛋白中的9个插入位点,如下表15中所示。在两个表位中使用间隔区(SEQ ID NO:97:TSYWKGS)而将所述两个表位置于位置10处。间隔区具有在连续表位之间产生物理空间的功能,有助于防止与抗体的相互作用。
表15
上述这些多氨基酸的序列与Rx蛋白的组合产生RxYFIgG蛋白。对应于包含表位YFIgGEp 1至YFIgGEp 10的RxYFIgG基因的氨基酸序列描述于SEQ ID no.75。对应于RxYFIgG蛋白的基因,本文中称为RxYFIgG基因,描述于核苷酸序列SEQ ID no.76。
通过现有技术分子生物学方法、使用用于酶NdeI和Xhol的限制性位点将合成基因RxYFIgG引入pET28a质粒。为了识别合成基因是否与为RxYFIgG设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化和其后的测序技术来分析质粒材料,如在PlatCruzi中先前所描述的。
将分析的具有RxYFIgG的正确序列的质粒转移至大肠杆菌菌株BL21,以产生RxYFIgG蛋白。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在37℃下在LB培养基中生长过夜,然后再接种在具有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并在37℃下维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于2mL的具有CelLytic(0.5x)的PBS中,在4℃下1小时。在另一次离心后,收集上清液并将沉淀重悬于与上清液相同体积的8M尿素溶液(pH8.0)中。将相等的体积上样至SDS-PAGE凝胶(11%,表5)。通过SDS-PAGE电泳检验蛋白RxYFIgG以证明其生产并确定其在可溶性和不溶性部分之间的分布。如图11中所示,第9列和第10列(箭头)显示RxYFIgG作为可溶性和不溶性产生,在不溶性部分中具有更高比例。
实施例17–TxNeuza蛋白的开发
基因操纵容器蛋白“Tx”以具有来自作为人中呼吸过敏(respiratory allergy)的主要原因的屋尘螨(Dermatophogoides pteronyssinus)的t细胞表位,我们在本文中称为TxNeuza平台。对应于TxNeuza蛋白的基因,本文中称为TxNeuza基因,描述于核苷酸序列SEQID NO:89。
从屋尘螨的T细胞多氨基酸序列的作图研究,考虑到它们对于由屋尘螨导致的过敏的诊断潜力,从可获得的现有技术文献选择多氨基酸序列(Hinz等,Clin Exp Allergy45:1601-1612,2015;Oseroff等,Clin Exp Allergy 47:577-592,2017)。选择本文中称为NeuzaEp1至NeuzaEp9的9条多氨基酸序列用于插入至Tx蛋白中的9个插入位点,如下表16中所示。在本实施例中,在两个表位中使用间隔区(SEQ ID NO:98:GGSG)而将两个表位置于位置12处。
表16
上述这些表位与Tx蛋白的序列的组合产生TxNeuza蛋白。对应于包含表位NeuzaEp1至NeuzaEp9的TxNeuza基因的氨基酸序列描述于SEQ ID NO:88。
通过现有技术分子生物学方法、使用用于酶NdeI和Xhol的限制性位点将合成基因TxNeuza引入pET28a质粒。为了识别合成基因是否与为TxNeuza设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化和其后的测序技术来分析质粒材料,如在PlatCruzi中先前所描述的。
将分析的具有TxNeuza的正确序列的质粒转移至大肠杆菌菌株BL21,以产生TxNeuza蛋白。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在37℃下在LB培养基中生长过夜,然后再接种在具有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并在37℃下维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于2mL的具有CelLytic(0.5x)的PBS中,在4℃下1小时。在另一次离心后,收集上清液并将沉淀重悬于与上清液相同体积的8M尿素溶液(pH8.0)中。将相等的体积上样至SDS-PAGE凝胶(11%,表5)。通过SDS-PAGE检验TxNeuza蛋白以证明其生产并确定其在可溶性和不溶性部分之间的分布。如图11中所示,第7列和第8列(箭头)显示TxNeuza作为不溶性产生。
实施例18–TxCruzi蛋白的开发
考虑到对于用于恰加斯病的诊断试验的实验特异性和灵敏度,从可获得的现有技术文献选择克氏锥虫多氨基酸序列(Balouz,等,Clin Vaccine Immunol 22,304-312,2015;Alvarez,等,Infect Immun 69,7946-7949,2001;Fernandez-Villegas,等,JAntimicrob Chemother 71,2005-2009,2016;Thomas,等,Clin Vaccine Immunol 19,167-173,2012)。选择10条多氨基酸序列用于插入至“Tx”蛋白中的10个插入位点,如下表17中所示,所述10条多氨基酸序列本文中称为TcEp 1、TcEp 3、TcEp 4、TcEp 6、TcEp 8、TcEp 9、TcEp 10、TcEp 11、TcEp 12、和TcEp 13。在两个表位中使用间隔子(SEQ ID NO:99:GGASG)而将所述两个表位置于位置12。
表17
在选择克氏锥虫多氨基酸序列后,通过化学合成、通过连接基因合成方法产生对应于TxCruzi蛋白的合成基因,并插入至质粒用于实验。对应于包含表位TcEp 1、TcEp 3、TcEp 4、TcEp 6、TcEp 8、TcEp 9、TcEp 10、TcEp 11、TcEp 12和TcEp 13的TxCruzi基因的核苷酸序列描述于SEQ ID no.91。
上述这些表位的序列与Tx蛋白的序列的组合产生TxCruzi蛋白。对应于包含表位TcEp 1、TcEp 3、TcEp 4、TcEp 6、TcEp 8、TcEp 9、TcEp 10、TcEp 11、TcEp 12、和TcEp 13的TxCruzi基因的氨基酸序列描述于SEQ ID NO:90。
通过现有技术分子生物学方法、使用用于酶NdeI和Xhol的限制性位点将合成基因引入pET28a质粒。为了识别合成基因是否与为TxCruzi蛋白设计的序列配对,转化大肠杆菌的DH5α菌株并通过限制性酶消化技术、然后测序来分析质粒材料,如在PlatCruzi中已详细描述的。
将分析的具有TxCruzi的正确序列的质粒转移至大肠杆菌菌株BL21,以产生TxCruzi蛋白。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株可表达T7 RNA聚合酶。BL21菌株在37℃下在LB培养基中生长过夜,然后再接种在具有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。然后,将IPTG(q.s.p.1mM)添加至培养物并在37℃下维持相同的培养条件另外的3小时。
对培养物进行离心并将沉淀重悬于2mL的具有CelLytic(0.5x)的PBS中,在4℃下1小时。在另一次离心后,收集上清液并将沉淀重悬于与上清液相同体积的8M尿素溶液(pH8.0)中。将相等的体积上样至SDS-PAGE凝胶(11%,表5)。
通过SDS-PAGE检验TxCruzi蛋白以证明其生产并确定其在可溶性和不溶性部分之间的分布。如图11中所示,第3列和第4列(箭头)显示TxCruzi作为可溶性和不溶性产生。与PlatCruzi(第1列和第2列)相比,TxCruzi显示产生的可溶性蛋白的比例的提高,这可归因于Tx作为容器蛋白的使用。
实施例19-SARS-CoV-2肽文库在纤维素膜上的合成和与来自SARS-CoV-2阳性和阴性个体的血清的反应性
基于在中国武汉市分离并公布于GenBank数据库(https://www.ncbi.nlm.nih.gov/nuccore/MN908947.3?report=genbank)的SARS-CoV-2的基因组序列,合成覆盖SARS-CoV-2病毒的ORF3a、ORF6、ORF7、ORF8、ORF10、N、M、S、E的所有蛋白质编码区域的多肽文库,并如下注释:
未由SARS-CoV-2病毒编码的4种多肽包含在肽文库列表中,以表示用于人血清的反应性的阳性对照。表18中,A1,V5(IHLVNNESSEVIVHK,破伤风梭菌(Clostriduium tetani)前体肽),A2,V6(GYPKDGNAFNNLDR,破伤风梭菌),A3,V7(KEVPALTAVETGATG,人骨髓灰质炎病毒),A4,V8(YPYDVPDYAGYPYD,三血凝素肽(triple hemagglutinin peptide))用作这样的对照。表19和20中,A1,V4(IHLVNNESSEVIVHK,破伤风梭菌前体肽),A2,V5(GYPKDGNAFNNLDR,破伤风梭菌),A3,V6(KEVPALTAVETGATG,人骨髓灰质炎病毒),A4,V8(YPYDVPDYAGYPYD,三血凝素肽)用作这样的对照。
作为阴性对照,无肽斑点反应物用于表18中的A5、A6、K20、K21、N3、N4、O24、P1、P13、P14、Q14、Q15、R15、R16、V3、V4、V9-V24、W14,和表19和表20中的A5、K19、K20、N2、N3、O23、O24、P12、P13、Q13、Q14、R15、R15、V2、V3、V17、V18。
合成线性多氨基酸的关系示于表18、表19、和表20。
表18–用于图12中对来自患者血清的IgM反应性表位作图的合成的SARS-CoV-2多氨基酸的列表。
表19-用于图13中对来自患者血清的IgG反应性表位作图的合成的SARS-CoV-2多氨基酸的列表。
表20-用于图14中对来自患者血清的IgA反应性表位作图的合成的SARS-CoV-2多氨基酸的列表。
实施例20–纤维素膜上SARS-CoV-2的多氨基酸文库的合成
根据制造商的说明、使用Auto-Spot Robot ASP-222 Auto-Spot Robot、根据标准斑点合成技术在Amino-PEG500-UC540纤维素膜上制备描述于实施例19的多肽文库。合成具有15个残基的长度和10个相邻残基的重叠的多氨基酸,覆盖蛋白质的完整长度。
合成后,用在TBS-T缓冲液(50mM Tris、NaCl;136mM,2mM KCl;0.05%,Tween-20;pH 7.4)中制备的1.5%BSA(牛血清白蛋白)封闭膜的游离位点90分钟。然后,用患者血清(n=3;1:100,在含有0.75%BSA的TBS-T中稀释)孵育膜,并用TBS-T洗涤4次。其后,用山羊IgG抗IgM(mu,KPL)、抗IgG(H+L链,Thermo Scientific)或抗人IgA(α链特异性,Calbiochem)(1:5000,在TBS-T中制备)孵育膜1.5h,然后用TBS-T和CBS(含有50mM NaCl的柠檬酸钠缓冲液,pH 7.0)洗涤。然后,添加化学发光底物(0.25mM)和Nitro-Block-IITMEnhancer(Applied Biosystems,USA)以完成反应。
在Odyssey FC设备(LI-COR Bioscience)上检测化学发光信号并使用TotalLabTL100软件(v 2009,Nonlinear Dynamics,USA)量化信号的强度。用Microsoft Excel程序分析数据,仅将信号强度(SI)大于或等于在各个膜中斑点的集合中获得的最高值的30%的斑点包含在多氨基酸的特征中。作为阴性对照,使用各个膜的背景信号强度。
实施例21–来自SARS-CoV-2的支链多氨基酸的合成
根据制造商的说明、使用Schimadzu合成器型号PSS8上的F-moc固相多氨基酸合成策略合成多个支链多氨基酸(SARS-X1-SARS-X8)。Wang Kcore树脂(双赖氨酸核,K4)(Novabiochem)用作用于支链多氨基酸的合成的固体支撑物。待缀合的第一个氨基酸是位于多肽序列的C末端部分的氨基酸,最后一个位于N-起始。在完成支链多氨基酸的合成的所有循环后,根据用于生产合成多氨基酸和氨基酸侧链的保护基团的去保护的现有技术使用的标准过程(Guy和Fields,Methods Emzymol 289,67-83,1997)、通过由裂解混合物(cleavage cocktail)(三氟乙酸、三异丙基硅烷、和乙二醇)处理,所述支链多氨基酸从固体支撑物脱离。对于合成的质量控制,通过HPLC和MALDI-TOF分析各个多氨基酸。
SARS-CoV-2的S蛋白的合成多氨基酸X1、X2和X5分别包括SEQ ID NO:100、101和104。SARS-CoV-2的N蛋白的合成多氨基酸X3和X6分别包括SEQ ID NO:102和105。SARS-CoV-2的E蛋白的合成多氨基酸X4包括SEQ ID NO:103。由S和Se基因之间的开放阅读框(ORF8)编码的SARS-CoV-2蛋白的合成多氨基酸X7和X8分别包括SEQ ID NO:106和107。
在S和Se基因之间的小开放阅读框(ORF)中发现编码X8蛋白的基因。在M和N基因之间的ORF的组成中发现编码ORF6、X4和X5蛋白的基因。
合成支链多肽的列表示于表21。
表21-SARS-CoV-2蛋白的合成支链肽
实施例22–人血清样品组
将134个人血清样品分为5组。所述组为:
-组0:来自供血库(HEMORIO)的2016年之前获得的10个健康人血清样品(血清#1-#10);
-组1:来自根据WHO病例定义确定的“无症状SARS患者”的26个血清样品(#1-#26);
-组2:来自“疑似患者”的24个血清样品(#27-#50);
-组3:来自根据WHO病例定义确定的“SARS住院患者(严重疾病)”的38个血清样品(#51-#88);
-组4:来自“对SARS免疫保护的患者”的36个血清样品(#89-#124)。
血清#1-#26,高体温恢复至正常温度,对SARS-CoV-2为RT-PCR+,抗SARS-CoV-2抗体的SD快速检测(Standard diagnostic Inc.)为阴性。
#27-#50:患者具有对SARS-CoV-2诊断为RT-PCR+,且抗SARS-CoV-2抗体SD快速检测为阴性。
#51-#88:住院个体具有恶化的SARS-CoV-2的体征和症状,快速RT-PCR检测+,对于抗SARS-CoV-2抗体的SD为阳性。
#89-#124:免疫保护的个体定义为康复的患者,住院或非住院的,所述患者诊断为SARS-CoV-2阳性或不诊断为SARS-CoV-2阳性,有时未通过RT-PCR+的诊断,但显示特征症状。
实施例23-SARS-CoV-2相关IgM多氨基酸的识别
为了识别可由抗SARS-CoV-2IgM抗体特异性识别的潜在多氨基酸,通过包括S、ORF3a、M、ORF6、ORF7、ORF8、N、E、ORF10的所有区域和对照多氨基酸的SARS-CoV-2斑点多肽文库合成阵列来分析来自感染的患者的血清样品。
肽阵列用于检测来自感染的个体的人血清对多氨基酸的潜在结合活性。肽阵列覆盖15个氨基酸长度的肽序列,在相邻斑点中具有10个氨基酸重叠。这样的线性多氨基酸包括以下SARS-CoV-2蛋白:
-刺突蛋白(S):aa 1-1273(斑点A7-K19),
-ORF3a蛋白(ORF3):aa 1-275(斑点K22-N2),
-膜糖蛋白(M):aa 1-222(斑点N5-O23),
-ORF6蛋白(ORF6):aa 1-61(斑点P2-P12),
-ORF7蛋白(ORF7):aa 1-121(斑点P15-Q13),
-ORF8蛋白(ORF8):aa 1-121(斑点Q16-R17),
-核衣壳蛋白(N):aa 1-419(斑点R20-V17),
-包膜蛋白(E):aa 1-75(斑点W1-W13)
-ORF10蛋白(ORF10):aa 1-38(斑点W15-W20)
-阳性对照多氨基酸:A1和V5(破伤风梭菌前体肽),A2和V6(破伤风梭菌前体肽),A3和V7(人骨髓灰质炎病毒肽),A4和V8(三血凝素表位)
-无反应性斑点作为阴性对照。
使用在纤维素膜上共价合成的多氨基酸(斑点)和来自患者#55、#60和#74(组3)的血清池(n=3),分析人抗IgM抗体对各种SARS-CoV-2(S、ORF3a、M、ORF6、ORF7、ORF8、N、E、ORF10)合成多氨基酸和对照多氨基酸(实施例19和20)的血清学免疫应答,如图12中所示,由表18补充。
图15A至15I显示来自采用山羊抗人IgM二抗显色的、用人血清孵育的膜斑点的信号量化结果。
当由抗人IgM抗体显色时,人血清已显示与来自不同病毒蛋白的多氨基酸的显著反应性,如图15A至15I中所示,表明即使在感染的初期阶段,大量的不同多氨基酸也具有用于诊断疾病的极大潜力。
实施例24–SARS-相关IgG表位的识别
为了识别可由抗SARS-CoV-2IgG抗体特异性识别的潜在表位,通过包括S、ORF3a、M、ORF6、ORF7、ORF8、N、E、ORF10的所有区域和对照多氨基酸的SARS-CoV-2斑点多氨基酸文库合成阵列来分析来自感染的患者的血清样品。
肽阵列用于检测来自感染的个体的人血清对多氨基酸的潜在结合活性。肽阵列覆盖15个氨基酸长度的肽序列,在相邻斑点中具有10个氨基酸重叠。这样的线性多氨基酸包括以下SARS-CoV-2蛋白:
-ORF3a蛋白(OF3a):aa 1-275(斑点A7-C11),
-膜糖蛋白(M):aa 1-222(斑点C14-E8),
-ORF6蛋白(OF6):aa 1-61(斑点E11-E21),
-ORF7蛋白(OF7(:aa 1-121(斑点E24-F22),
-ORF8蛋白(OF8):aa 1-121(斑点G1-G23),
-刺突蛋白(S):aa 1-1273(斑点H1-R13),
-核衣壳蛋白(N):aa 1-419(斑点R16-V1),
-包膜蛋白(E):aa 1-75(斑点W1-W13),
-ORF10蛋白(OF10):aa 1-38(斑点W15-W20),
-阳性对照多肽:A1和V4(破伤风梭菌前体肽),A2和V5(破伤风梭菌前体肽),A3和V6(人骨髓灰质炎病毒肽),A4和V7(三血凝素表位)
-无反应物斑点作为阴性对照
使用在纤维素膜上共价合成的肽(斑点)和来自患者#55、#60和#74(组3)的血清池(n=3),分析IgG抗体对各种SARS-CoV-2(ORF3a、M、ORF6、ORF7、ORF8、S、N、E、ORF10)合成多氨基酸和对照多氨基酸的血清学免疫应答,如图13中所示,由表19补充。
图16A至16H显示来自采用山羊抗人IgG二抗显色的、用人血清孵育的膜斑点的信号量化结果。
当由抗人IgG抗体显色时,人血清已显示与来自不同病毒蛋白的多氨基酸的显著反应性,如图16A至16H中所示,表明即使在感染的急性期之后的阶段中,大量的不同多氨基酸具有用于诊断疾病的极大潜力。
实施例25–与SARS相关的多氨基酸IgA的识别
为了识别可由抗SARS-CoV-2IgA抗体特异性识别的潜在多氨基酸,通过包括S、ORF3a、M、ORF6、ORF7、ORF8、N、E、ORF10的所有区域和对照多氨基酸的SARS-CoV-2斑点多氨基酸文库合成阵列来分析来自感染的患者的血清样品。
肽阵列用于检测来自感染的个体的人血清对多氨基酸的潜在结合活性。肽阵列覆盖15个氨基酸长度的肽序列,在相邻斑点中具有10个氨基酸重叠。这样的线性多氨基酸包括以下SARS-CoV-2蛋白:
-刺突蛋白(S):aa 1-1273(斑点A6-K18),
-ORF3a蛋白(ORF3):aa 1-275(斑点K21-N1),
-膜糖蛋白(M):aa 1-222(N4-O22),
-ORF6蛋白(ORF6):aa 1-61(P2-P12),
-ORF7蛋白(ORF7):aa 1-121(P15-Q13),
-ORF8蛋白(ORF8):aa 1-121(Q16-R17),
-核衣壳蛋白(N):aa 1-419(斑点R20-V17),
-包膜蛋白(E):aa 1-75(斑点W1-W-13),
-ORF10蛋白(ORF10):aa 1-38(斑点W15-W20),
-阳性对照多肽:A1和V4(破伤风梭菌前体肽),A2和V5(破伤风梭菌前体肽),A3和V6(人骨髓灰质炎病毒肽),A4和V7(三血凝素表位),
-无反应物斑点作为阴性对照。
使用在纤维素膜上共价合成的肽(斑点)和来自患者#55、#60和#74(组3)的血清池(n=3),分析IgA抗体对各种SARS-CoV-2(ORF3a、M、ORF6、ORF7、ORF8、S、N、E、ORF10)的合成多氨基酸和对照多氨基酸的B细胞免疫应答,如图14中所示,由表20补充。
图17A至17I显示来自采用山羊IgG抗人IgA二抗显色的、用人血清孵育的膜斑点的信号量化结果。
当由抗人IgA抗体显色时,人血清已显示与不同病毒蛋白的多氨基酸的显著反应性,如图17A至17I中所示,表明通过主要存在于粘膜中的这类抗体,大量的不同多氨基酸具有用于诊断疾病的极大潜力。
实施例26–用于检测抗SARS-CoV-2抗体的酶联免疫吸附测定ELISA
酶联免疫吸附测定(ELISA)用于在患者血清中筛选抗SARS-CoV-2抗体。通过用1μg/孔的支链多氨基酸包被96孔聚苯乙烯板来进行ELISA。为了比较结果,平行且同时地进行各组的实验。为了减少试验之间的性能可能的差异变化,采用反应性指数(RI),其定义为从截断O.D.450减去靶标的O.D.450。在PBS/BSA 1%和二抗山羊抗人IgM(Merck-Sigma)、8000x生物素标记的山羊抗人IgG(Merck-Sigma)中将原始人血清稀释100倍(100X),接着用HRP标记的高灵敏度中性亲和素(neutravidin)(Thermo Fisher Scientific)孵育。由碱性磷酸酶标记的山羊抗人IgA(KPL)显色抗IgA应答。TMB(3,3’,5,5’四甲基联苯胺)用作底物(Thermo Fisher Scientific),当反应性指数大于1时,将免疫应答定义为显著提高的。
结果显示,支链多氨基酸SARS-X1至SARS-X8针对抗SARS-CoV2抗体的反应性有差异,这些差异与检测的人抗体的种类(IgM、IgG或IgA)和诊断有SARS-CoV2的患者的状态相关,如从图18至23的分析中可以看出。观察这样的差异允许设计诊断试验,可提供比简单的对于抗SARS-CoV2抗体为阳性或阴性诊断更准确或可靠的信息。因此,除了检测IgM、IgG、或IgA抗体以外,诊断试验还可设计成指示个体是否应住院,即使在不存在症状的情况下。
实施例27–用于SARS-CoV-2的容器蛋白的开发
基因操纵“Tx”容器蛋白以具有SARS-CoV-2表位。选择来自SARS-CoV-2感染的个体的血清的反应性表位用于构建8种Tx蛋白:Ag-COVID19、Ag COVID19(H)、Tx-SARS2-IgM、Tx-SARS2-IgG、Tx-SARS2-G/M、Tx-SARS2-IgA、Tx-SARS2-Universal和Tx-SARS-G5(非RBD)。
对应于Ag-COVID19、Ag COVID19(H)、Tx-SARS2-IgM、Tx-SARS2-IgG、Tx-SARS2-G/M、Tx-SARS2-IgA、Tx-SARS2-Universal、和Tx-SARS-G5(非RBD)蛋白的基因,本文中分别称为Ag-COVID19基因、Ag-COVID19(H)基因、Tx-SARS2-IgM基因、Tx-SARS2-IgG基因、Tx-SARS2-G/M基因、Tx-SARS2-IgA基因、Tx-SARS2-Universal基因、和Tx-SARS-G5(非RBD)基因,描述于核苷酸序列SEQ ID NO:108至SEQ ID NO:115。对应于Ag-COVID19、Ag COVID19(H)、Tx-SARS2-IgM、Tx-SARS2-IgG、Tx-SARS2-G/M、Tx-SARS2-IgA、Tx-SARS2-Universal和Tx-SARS-G5(无RBD)蛋白的氨基酸序列分别描述于SEQ ID NO 116至123。
从SARS-CoV-2表位序列作图研究,考虑到如实施例19至26中所阐明的它们的诊断潜力,具有多氨基酸的上述8种蛋白质示于表22至28。
表22-Ag-COVID19和Ag COVID19蛋白(H)
表23-Tx-SARS2-IgM
表24-Tx-SARS2-IgG
表25-Tx-SARS2-G/M
表26-Tx-SARS2-IgA
表27-Tx-SARS2-Universal
表28-Tx-SARS2-G5
实施例28具有来自SARS-CoV-2的多氨基酸的容器蛋白的表达
使用利用针对BamHI和XhoI酶的限制性位点、具有编码各蛋白的基因的pET24质粒,表达Ag-COVID19、Ag-COVID19(H)、Tx-SARS2-IgM、Tx-SARS2-IgG、Tx-SARS2-G/M、Tx-SARS2-IgA、Tx-SARS2-Universal和Tx-SARS-G5(非RBD)蛋白。将包含针对特定蛋白的基因的各质粒转移至大肠杆菌BL21菌株,以促进上述列出的8种不同蛋白的表达。
将菌株在LB培养基中生长过夜,然后再接种在添加有卡那霉素(30μg/ml)的相同培养基中,在200rpm下的摇床上直至其达到0.6-0.8(600nm)的浊度的光密度。当由异丙基β-D-1-硫代半乳糖苷(IPTG)诱导时,BL21菌株表达T7 RNA聚合酶。然后,将IPTG(q.s.p.1mM)添加至培养物并在37℃下维持相同的培养条件另外的3小时。
对各细菌菌株的培养物进行离心并将沉淀重悬于在150mM NaCl和50mM Tris,pH8.0中的10%CelLyticTM(Sigma,BR)中。对重组蛋白的试样(1μg/孔)进行含有SDS的聚丙烯酰胺凝胶电泳(SDS-PAGE)(Laemmli,Nature 227:680-685,1970)。分别在4%和11%的丙烯酰胺浓度下制备浓缩凝胶(浓缩胶)和分离凝胶(分离胶)(表5,下文)。在变性条件下,在62.5mM Tris-HCl缓冲液,pH 6.8、2%SDS、5%β-巯基乙醇、10%甘油中制备样品,并在95℃下煮5分钟(Hames BD,Gel electrophoresis of proteins:a practicalapproach.3.Ed.Oxford.1998)。电泳后,通过用考马斯亮蓝Simply Blue R250(ThermoFisher,BR)染色来检测蛋白。标记物PageRuler Plus Prestained Standards用作分子量参照(ThermoFisher,BR)。图24,显示Ag-COVID19(第3列)、Ag-COVID19(H)(第4列)、Tx-SARS2-IgM(第5列)、Tx-SARS2-IgG(第6列)、Tx-SARS2-G/M(第7列)、Tx-SARS2-IgA(第8列)、Tx-SARS2-Universal(第9列)和Tx-SARS-G5(非RBD)(第10列)的条带。第1列显示分子量标记物:A)250kDa;B)130kDa;C)100kDa;D)70kDa;E)55kDa;F)35kDa和G)25kDa。第2列显示未诱导的细菌的总提取物。
可选地,还对培养物进行离心并将沉淀重悬于尿素缓冲液(100mM NaH2PO4、10mMTris-base、8M尿素,pH 8.0)中。通过镍亲和性柱(HisTrapTM,1mL,GE Healthcare LifeSciences)mL每分钟对溶液进行层析,所述柱先前在缓冲液A(50mM Tris-HCl,pH 8.0、100mM NaCl和5mM咪唑)中平衡。结合后,用10mL的缓冲液A洗涤树脂。以0.7mL/分钟的流动速率在具有75mM、200mM、和500mM咪唑的缓冲液B(50mM Tris-HCl,pH 8.0、100mM NaCl)中梯度洗脱蛋白45分钟。图25显示对应于具有六个组氨酸尾的Ag-COVID19蛋白的模式,表明200mM洗脱浓度。图26显示对应于通过使用200mM咪唑的亲和性纯化的SARS2-G5蛋白的模式(由75mM进行的洗脱显示污染物)。
结果显示,Tx容器蛋白可很容易地用于产生新的且不同的蛋白。此外,可使用相同的表达方案进行具有不同多氨基酸的不同容器蛋白的表达,以极大地节约投入、时间、和基础设施。六个组氨酸尾的包含显示为用于以高纯度水平纯化的潜在促进剂。
实施例29–使用Ag-COVID19和SARS2-G5蛋白检测抗SARS-CoV-2抗体的酶联免疫吸附测定(ELISA)
酶联免疫吸附测定(ELISA)用于筛选抗SARS-CoV-2抗体的存在。针对一组来自受到SARS-CoV-2病毒感染影响的个体的血清,评价Ag-COVID19和SARS2-G5蛋白的性能。
通过在4℃下、用Ag-COVID19蛋白(图27)或Tx-SARS2-G5蛋白(图28)的溶液(0.3M尿素,pH 8.0)以1μg/孔包被96孔聚苯乙烯板12-18小时来进行ELISA。用添加有Tween 20(PBS-T,10mM磷酸钠-Na3PO4,150mM氯化钠–NaCl和0.05%Tween-20,pH 7.4)的盐水-磷酸盐缓冲液(PBS)溶液洗涤孔,然后在37℃下用含有5%(重量/体积)脱脂奶粉的1x PBS缓冲液孵育2小时。
然后,用PBS-T缓冲液洗涤孔3次,并在37℃下、用在PBS/BSA 1%中1:100稀释的人血清样品孵育1小时。孵育后,用PBS-T洗涤孔3次,然后在37℃下用以1:8000稀释的生物素标记的山羊抗人IgG抗体(Merck-Sigma)孵育1小时。其后,添加HRP标记的高灵敏度中性亲和素(Thermo Fisher Scientific)。再次用PBS-T缓冲液洗涤孔3次并使用TMB底物(3.3’,5.5’四甲基联苯胺,Thermo Fisher Scientific)。避光下30分钟后,在ELISA读板机中测定405nm处的吸光度。
结果显示,通过表明优异的灵敏度和特异性指数,Ag-COVID19蛋白(图27)和Tx-SARS2-G5蛋白(图28)已证明有利地用于检测针对SARS-CoV-2的抗体。如从图27和28可以看出的,具有来自SARS-CoV-2的多氨基酸的蛋白在来自SARS-CoV-2流行前收集的个体、健康或受到例如登革热、疟疾、和梅毒等疾病影响的个体的血清中未检测到抗体。不同地,蛋白质在来自对SARS-CoV-2诊断为阳性(有症状或无症状)的个体、住院或已康复的患者的血清中检测到抗体。
实施例30-Ag-COVID19蛋白作为疫苗组合物
根据本专利申请中所描述的方案生产并纯化Ag-COVID19蛋白。在第0、14、21、和28天,用悬浮于弗氏不完全佐剂(25μl)中的在25μl的PBS中的10μg的Ag-COVID19蛋白对三只小鼠进行接种。使用接种PBS的动物进行阴性对照。在每次再接种前收集来自动物的血液样品并进行ELISA。通过离心从收集的血液分离血浆并进行系列稀释以进行抗体测定(图29)。结果显示,在自第一次注射后四周后,针对Ag-COVID19的优异的抗体产生。
实施例31-Ag-COVID19蛋白用于抗SARS-CoV-2抗体的纯化的用途
使用抗体亲和性原理进行来自诊断有COVID19的患者的血清的抗SARS-CoV-2抗体的纯化。Ag-COVID19蛋白缀合至由CNBr(GE Healthcare,USA)激活的SepharoseTM 4B。在10mL PBS中稀释来自SARS-CoV-2阳性患者的10mL血清样品,并使其经受Sepharose-Ag-COVID19 1小时。然后将混合物置于层析柱。在溶液穿过柱后,将10mL的PBS添加至层析系统,然后添加5mL的pH 4的100mM柠檬酸钠缓冲液。随着从柱回收,顺序收集0.5ml的级分并通过280nm处的分光光度法定量抗体的存在。将各级分的吸光度转换为蛋白质浓度并作为级分的体积的函数作图。
结果表明,Ag-COVID19蛋白可有用地作为来自先前感染有SARS-CoV-2的患者的抗体的亲和性纯化的内参neican(input)(图30),表明其在产生用于被动免疫以应对COVID-19流行病的可用的内参中的重要性。
序列表
<110> 奥斯瓦道·克鲁兹基金会
<120> 蛋白质容器、多核苷酸、载体、表达盒、细胞、容器的生产方法、病原体识别或疾病诊断方法、容器的用途、和诊断试剂盒
<130> P139205
<150> BR102019017792-6
<151> 27-08-2019
<160> 163
<170> PatentIn 版本 3.5
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catatggtgg ctagcaaagg tgaagaactg ttcaccggtg ttgttccgat cctgattgaa 60
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Gln Thr Val Leu Ser Lys Asp Pro Asn Glu Leu Lys Arg Asp His Met
210 215 220
Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp
225 230 235 240
Glu Leu Tyr Lys Glu Phe
245
<210> 4
<211> 753
<212> DNA
<213> 人工序列
<400> 4
catatggtgg ctagcaaggg cgaggagctg ttcaccggcg tcgtccccat cctggtcgag 60
ctggacggcg acgttaacgg ccacaagttc tccgtccggg gcgagggcga gggcgacgcc 120
accatcggca agctgaccct gaagttcatc tgcaccaccg gcaagcttcc cgtcccctgg 180
cccaccctgg tcaccaccct gacctatggc gtccagtgct tcgcccggta tcccgaccac 240
atgaagcggc acgacttctt caagtccgcc atgcccgagg gctatgtcca ggagcggacc 300
atctccttca aggacgtcga tggcaagtat aagacccggg ccgtcgtcaa gttcgagggt 360
accgacaccc tggtcaaccg gatcgtcctg aagggcaccg acttcaagga ggacggcaac 420
atccttaagg gccacaagct ggagtataac ttcaactccc acaacgtcta tatcaccgcg 480
gacaaacaga agaacggcat caaggccaac ttcaccgtcc ggcacaacgt cgaggacgga 540
tccgtccagc tggccgacca ctatcagcag aacaccccca tcggcgacgg tccggtcctg 600
ctgcccgaca accactatct gtccacccag accgtcctgt ccaaggaccc gaacgagctc 660
aaacgggacc acatggtcct gctggagttc gtcaccgccg ccggcatcac cctgggcatg 720
gacgagctgt ataaggaatt ctaatgactc gag 753
<210> 5
<211> 15
<212> DNA
<213> 人工序列
<400> 5
catatggtgg ctagc 15
<210> 6
<211> 18
<212> DNA
<213> 人工序列
<400> 6
gaattctaat gactcgag 18
<210> 7
<211> 17
<212> PRT
<213> 人工序列
<400> 7
Lys Phe Ala Glu Leu Leu Glu Gln Gln Lys Asn Ala Gln Phe Pro Gly
1 5 10 15
Lys
<210> 8
<211> 7
<212> PRT
<213> 人工序列
<400> 8
Lys Ala Ala Ala Ala Pro Ala
1 5
<210> 9
<211> 7
<212> PRT
<213> 人工序列
<400> 9
Lys Ala Ala Ile Ala Pro Ala
1 5
<210> 10
<211> 15
<212> PRT
<213> 人工序列
<400> 10
Gly Asp Lys Pro Ser Pro Phe Gly Gln Ala Ala Ala Ala Asp Lys
1 5 10 15
<210> 11
<211> 9
<212> PRT
<213> 人工序列
<400> 11
Lys Gln Lys Ala Ala Glu Ala Thr Lys
1 5
<210> 12
<211> 10
<212> PRT
<213> 人工序列
<400> 12
Ala Glu Pro Lys Pro Ala Glu Pro Lys Ser
1 5 10
<210> 13
<211> 10
<212> PRT
<213> 人工序列
<400> 13
Ala Glu Pro Lys Ser Ala Glu Pro Lys Pro
1 5 10
<210> 14
<211> 15
<212> PRT
<213> 人工序列
<400> 14
Gly Thr Ser Glu Glu Gly Ser Arg Gly Gly Ser Ser Met Pro Ser
1 5 10 15
<210> 15
<211> 11
<212> PRT
<213> 人工序列
<400> 15
Ser Pro Phe Gly Gln Ala Ala Ala Gly Asp Lys
1 5 10
<210> 16
<211> 9
<212> PRT
<213> 人工序列
<400> 16
Lys Gln Arg Ala Ala Glu Ala Thr Lys
1 5
<210> 17
<211> 1128
<212> DNA
<213> 人工序列
<400> 17
atgaaattcg cggaactgct ggaacagcag aaaaacgcgc agttcccggg taaagctagc 60
aaaggtgaag aactgttcac cggtgttgtt ccgatcctga ttgaactgga cggtgacgtt 120
aacggtcaca aattctttgt tcgtggtgaa ggtgaaggtg acgcgaccat cggtaaactg 180
agtctgaaat tcatctgcac caccggtaag cttaaagcgg cggcggcgcc ggcgaagctt 240
ccggttccgt ggccgaccct ggttaccacc ctgacctacg gtgttcagtg cttctctcgt 300
tacccggacc acatgaaacg tcacgacttc ttcaaatctg cgatgccgga aggttacgtt 360
caggaacgta ccatctactt caaagacgtc aaagcggcga tcgcgccggc ggacgtcgac 420
ggtacttaca aaacccgtgc ggaagttaaa ttcgaaggta ccggtgacaa accgtctccg 480
ttcggtcagg cggcggcggc ggacaaaggt accgacaccc tggttaaccg tatcgttctg 540
aaaggcattg acttcaaaga agacggtaac atccttaagc agaaagcggc ggaagcgacc 600
aaacttaagg gtcacaaact ggaatacaac ttcaactctc acaacgttta catcaccgcg 660
gacgcggaac cgaaaccggc ggaaccgaaa tctaccgcgg acaaacagaa aaacggtatc 720
aaagcgaact tcaccgttcg tcacaacgtt gaagacggat ccgctgaacc gaaatctgcg 780
gaaccgaaac cgggatccgt tcagctggcg gaccactacc agcagaacac cccgatcggt 840
gacggtccgg gcacctctga agaaggttct cgtggtggtt cttctatgcc gtctgacggt 900
ccggttctgc tgccggacaa ccactacctg tctacccaga ccattctgct gaaagacccg 960
aacgagctct ctccgttcgg tcaggcggcg gcgggtgaca aagagctcaa acgtgaccac 1020
atggttctgc tggaatatgt tacggcggcg ggtatcaccc tgggtatgga cgaactgtac 1080
aaagaattca aacagcgtgc ggcggaagcg accaaatgat gactcgag 1128
<210> 18
<211> 372
<212> PRT
<213> 人工序列
<400> 18
Met Lys Phe Ala Glu Leu Leu Glu Gln Gln Lys Asn Ala Gln Phe Pro
1 5 10 15
Gly Lys Ala Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile
20 25 30
Leu Ile Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Phe Val Arg
35 40 45
Gly Glu Gly Glu Gly Asp Ala Thr Ile Gly Lys Leu Ser Leu Lys Phe
50 55 60
Ile Cys Thr Thr Gly Lys Leu Lys Ala Ala Ala Ala Pro Ala Lys Leu
65 70 75 80
Pro Val Pro Trp Pro Thr Leu Val Thr Thr Leu Thr Tyr Gly Val Gln
85 90 95
Cys Phe Ser Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe Lys
100 105 110
Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Tyr Phe Lys
115 120 125
Asp Val Lys Ala Ala Ile Ala Pro Ala Asp Val Asp Gly Thr Tyr Lys
130 135 140
Thr Arg Ala Glu Val Lys Phe Glu Gly Thr Gly Asp Lys Pro Ser Pro
145 150 155 160
Phe Gly Gln Ala Ala Ala Ala Asp Lys Gly Thr Asp Thr Leu Val Asn
165 170 175
Arg Ile Val Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu
180 185 190
Lys Gln Lys Ala Ala Glu Ala Thr Lys Leu Lys Gly His Lys Leu Glu
195 200 205
Tyr Asn Phe Asn Ser His Asn Val Tyr Ile Thr Ala Asp Ala Glu Pro
210 215 220
Lys Pro Ala Glu Pro Lys Ser Thr Ala Asp Lys Gln Lys Asn Gly Ile
225 230 235 240
Lys Ala Asn Phe Thr Val Arg His Asn Val Glu Asp Gly Ser Ala Glu
245 250 255
Pro Lys Ser Ala Glu Pro Lys Pro Gly Ser Val Gln Leu Ala Asp His
260 265 270
Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro Gly Thr Ser Glu Glu
275 280 285
Gly Ser Arg Gly Gly Ser Ser Met Pro Ser Asp Gly Pro Val Leu Leu
290 295 300
Pro Asp Asn His Tyr Leu Ser Thr Gln Thr Ile Leu Leu Lys Asp Pro
305 310 315 320
Asn Glu Leu Ser Pro Phe Gly Gln Ala Ala Ala Gly Asp Lys Glu Leu
325 330 335
Lys Arg Asp His Met Val Leu Leu Glu Tyr Val Thr Ala Ala Gly Ile
340 345 350
Thr Leu Gly Met Asp Glu Leu Tyr Lys Glu Phe Lys Gln Arg Ala Ala
355 360 365
Glu Ala Thr Lys
370
<210> 19
<211> 1029
<212> DNA
<213> 人工序列
<400> 19
atgctgcatg attttcgttc cgatgctagc aaaggtgaag aactgtttac cggtgttgtt 60
ccgattctgg ttgaactgga tggtgatgtt aatggccaca aattttcagt tcgtggtgaa 120
ggcgaaggtg atgcaaccat tggtaaactg accctgaaat ttatctgtac caccggtaag 180
cttccagttc cgtggccgac cctggttacc accctgacct atggtgttca gtgttttgca 240
cgttatccgg atcacatgaa acgccacgat tttttcaaaa gcgcaatgcc ggaaggttat 300
gttcaagaac gtaccattag ctttaaagac gtctgcaaac tgaaactgtg tggtgttctg 360
ggtctggacg tcgatggtaa atacaaaacc cgtgcagttg tgaaatttga gggtacctgt 420
aaactgaaac tgtgcggagt tagcggtctg ggtaccgata ccctggtgaa tcgtattgtt 480
ctgaaaggca ccgattttaa agaagatggc aacattctta agtgggttgc aatgcagacc 540
agcaatctta agggtcataa actggaatac aacttcaaca gccacaacgt gtatattacc 600
gcggatctgc acgattttca tagcgatacc gcggacaaac agaaaaatgg tattaaagcc 660
aattttaccg tgcggcataa tgttgaagat ggatcctgca aactgaaact gtgcggtgtg 720
cctggtctgg gatccgttca gctggcagat cattatcagc agaatacccc gattggtgac 780
ggtccggttg atgaacgtgg tctgtataaa gacggtccgg tgctgctgcc ggataatcat 840
tatctgagca cccagacagt tctgagcaaa gatccgaatg agctcctgca tgatctgcat 900
agtgatgagc tcaaacgtga tcacatggtt ctgctggaat ttgttaccgc agcaggtatt 960
accctgggta tggatgaact gtacaaagaa ttcaaaagtg tgcgcacctg gaacgaaatc 1020
taactcgag 1029
<210> 20
<211> 340
<212> PRT
<213> 人工序列
<400> 20
Met Leu His Asp Phe Arg Ser Asp Ala Ser Lys Gly Glu Glu Leu Phe
1 5 10 15
Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn Gly
20 25 30
His Lys Phe Ser Val Arg Gly Glu Gly Glu Gly Asp Ala Thr Ile Gly
35 40 45
Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val Pro
50 55 60
Trp Pro Thr Leu Val Thr Thr Leu Thr Tyr Gly Val Gln Cys Phe Ala
65 70 75 80
Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala Met
85 90 95
Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Val Cys
100 105 110
Lys Leu Lys Leu Cys Gly Val Leu Gly Leu Asp Val Asp Gly Lys Tyr
115 120 125
Lys Thr Arg Ala Val Val Lys Phe Glu Gly Thr Cys Lys Leu Lys Leu
130 135 140
Cys Gly Val Ser Gly Leu Gly Thr Asp Thr Leu Val Asn Arg Ile Val
145 150 155 160
Leu Lys Gly Thr Asp Phe Lys Glu Asp Gly Asn Ile Leu Lys Trp Val
165 170 175
Ala Met Gln Thr Ser Asn Leu Lys Gly His Lys Leu Glu Tyr Asn Phe
180 185 190
Asn Ser His Asn Val Tyr Ile Thr Ala Asp Leu His Asp Phe His Ser
195 200 205
Asp Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe Thr Val
210 215 220
Arg His Asn Val Glu Asp Gly Ser Cys Lys Leu Lys Leu Cys Gly Val
225 230 235 240
Pro Gly Leu Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr
245 250 255
Pro Ile Gly Asp Gly Pro Val Asp Glu Arg Gly Leu Tyr Lys Asp Gly
260 265 270
Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Thr Val Leu
275 280 285
Ser Lys Asp Pro Asn Glu Leu Leu His Asp Leu His Ser Asp Glu Leu
290 295 300
Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile
305 310 315 320
Thr Leu Gly Met Asp Glu Leu Tyr Lys Glu Phe Lys Ser Val Arg Thr
325 330 335
Trp Asn Glu Ile
340
<210> 21
<211> 11
<212> PRT
<213> 人工序列
<400> 21
Cys Lys Leu Lys Leu Cys Gly Val Leu Gly Leu
1 5 10
<210> 22
<211> 11
<212> PRT
<213> 人工序列
<400> 22
Cys Lys Leu Lys Leu Cys Gly Cys Ser Gly Leu
1 5 10
<210> 23
<211> 11
<212> PRT
<213> 人工序列
<400> 23
Cys Lys Leu Lys Leu Cys Gly Val Pro Gly Leu
1 5 10
<210> 24
<211> 8
<212> PRT
<213> 人工序列
<400> 24
Val Asp Glu Arg Gly Leu Tyr Lys
1 5
<210> 25
<211> 8
<212> PRT
<213> 人工序列
<400> 25
Trp Val Ala Met Gln Thr Ser Asn
1 5
<210> 26
<211> 9
<212> PRT
<213> 人工序列
<400> 26
Lys Ser Val Arg Thr Trp Asn Glu Ile
1 5
<210> 27
<211> 7
<212> PRT
<213> 人工序列
<400> 27
Leu His Asp Phe His Ser Asp
1 5
<210> 28
<211> 7
<212> PRT
<213> 人工序列
<400> 28
Leu His Asp Phe Arg Ser Asp
1 5
<210> 29
<211> 7
<212> PRT
<213> 人工序列
<400> 29
Leu His Asp Leu His Ser Asp
1 5
<210> 30
<211> 13
<212> PRT
<213> 人工序列
<400> 30
Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu Val
1 5 10
<210> 31
<211> 344
<212> PRT
<213> 人工序列
<400> 31
Met Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu Val Ala Ser
1 5 10 15
Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu Leu
20 25 30
Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Arg Gly Glu Gly Glu
35 40 45
Gly Asp Ala Thr Ile Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr
50 55 60
Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Leu Thr Tyr
65 70 75 80
Gly Val Gln Cys Phe Ala Arg Tyr Pro Asp His Met Lys Arg His Asp
85 90 95
Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile
100 105 110
Ser Phe Lys Asp Val Asp Gly Lys Tyr Lys Thr Arg Ala Val Val Lys
115 120 125
Phe Glu Gly Thr Asp Thr Leu Val Asn Arg Ile Val Leu Lys Gly Thr
130 135 140
Asp Phe Lys Glu Asp Gly Asn Ile Leu Lys Asp Val Leu Phe Thr Trp
145 150 155 160
Tyr Val Asp Gly Thr Glu Val Leu Lys Gly His Lys Leu Glu Tyr Asn
165 170 175
Phe Asn Ser His Asn Val Tyr Ile Thr Ala Asp Val Leu Phe Thr Trp
180 185 190
Tyr Val Asp Gly Thr Glu Val Gly Gly Ser Gly Thr Ala Asp Lys Gln
195 200 205
Lys Asn Gly Ile Lys Ala Asn Phe Thr Val Arg His Asn Val Glu Asp
210 215 220
Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly
225 230 235 240
Asp Gly Pro Gly Gly Ser Gly Asp Val Leu Phe Thr Trp Tyr Val Asp
245 250 255
Gly Thr Glu Val Asp Gly Pro Val Leu Leu Pro Asp Asn His Tyr Leu
260 265 270
Ser Thr Gln Thr Val Leu Ser Lys Asp Pro Asn Glu Leu Asp Val Leu
275 280 285
Phe Thr Trp Tyr Val Asp Gly Thr Glu Val Gly Gly Ser Gly Glu Leu
290 295 300
Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile
305 310 315 320
Thr Leu Gly Met Asp Glu Leu Tyr Lys Glu Phe Asp Val Leu Phe Thr
325 330 335
Trp Tyr Val Asp Gly Thr Glu Val
340
<210> 32
<211> 1035
<212> DNA
<213> 人工序列
<400> 32
atggatgttc tgtttacctg gtatgttgat ggcaccgaag tggctagcaa aggtgaagaa 60
ctgtttaccg gtgttgttcc gattctggtt gaactggatg gtgatgttaa tggccacaaa 120
ttttcagttc gtggtgaagg cgaaggtgat gcaaccattg gtaaactgac cctgaaattt 180
atctgtacca ccggtaagct tccagttccg tggccgaccc tggttaccac cctgacctat 240
ggtgttcagt gttttgcacg ttatccggat cacatgaaac gccacgattt tttcaaaagc 300
gcaatgccgg aaggttatgt tcaagaacgt accattagct tcaaagacgt cgatggtaaa 360
tacaaaaccc gtgccgttgt taaatttgaa ggtaccgata ccctggtgaa tcgtattgtt 420
ctgaaaggca ccgattttaa agaagatggc aacattctta aggacgtgct gttcacatgg 480
tatgtggacg gtacagaagt tcttaagggt cacaaactgg aatacaactt taacagccac 540
aacgtgtata ttaccgcgga cgtactgttt acgtggtacg tagacggaac ggaagttggt 600
ggtagcggca ccgcggacaa acagaaaaat ggtattaaag ccaattttac cgtgcggcat 660
aatgttgaag atggatccgt tcagctggca gatcattatc agcagaatac cccgattggt 720
gacggtccgg gtggttcagg tgatgtcctg ttcacttggt acgtcgatgg aaccgaggtg 780
gacggtccgg ttctgctgcc ggataatcat tatctgagca cccagaccgt tctgagcaaa 840
gatccgaatg agctcgatgt actgttcacg tggtatgtgg atgggactga agtgggtggt 900
agtggtgagc tcaaacgtga tcacatggtg ctgctggaat ttgttaccgc agcaggtatt 960
accctgggta tggatgaact gtataaagaa ttcgatgtgc tgtttacttg gtacgtggac 1020
gggactgagg tttaa 1035
<210> 33
<211> 380
<212> PRT
<213> 人工序列
<400> 33
Met Tyr Ile Glu Lys Asp Asp Ser Asp Ala Leu Lys Ala Leu Phe Ala
1 5 10 15
Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu
20 25 30
Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Arg Gly Glu Gly
35 40 45
Glu Gly Asp Ala Thr Ile Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr
50 55 60
Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Leu Thr
65 70 75 80
Tyr Gly Val Gln Cys Phe Ala Arg Tyr Pro Asp His Met Lys Arg His
85 90 95
Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr
100 105 110
Ile Ser Phe Lys Asp Val Gly Asn Phe Met Val Leu Ser Val Asp Asp
115 120 125
Val Asp Gly Lys Tyr Lys Thr Arg Ala Val Val Lys Phe Glu Gly Thr
130 135 140
Gly Asn Phe Met Val Leu Ser Val Asp Asp Gly Thr Asp Thr Leu Val
145 150 155 160
Asn Arg Ile Val Leu Lys Gly Thr Asp Phe Lys Glu Asp Gly Asn Ile
165 170 175
Leu Lys Thr Ser Arg Pro Met Val Asp Leu Thr Phe Gly Gly Val Gln
180 185 190
Leu Lys Gly His Lys Leu Glu Tyr Asn Phe Asn Ser His Asn Val Tyr
195 200 205
Ile Thr Ala Asp Lys Thr Ser Arg Pro Met Val Asp Leu Thr Phe Gly
210 215 220
Gly Val Gln Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe
225 230 235 240
Thr Val Arg His Asn Val Glu Asp Gly Ser Ile Phe Asn Asp Val Pro
245 250 255
Gln Arg Thr Thr Ser Thr Phe Asp Pro Gly Ser Val Gln Leu Ala Asp
260 265 270
His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro Ile Phe Asn Asp
275 280 285
Val Pro Gln Arg Thr Thr Ser Thr Phe Asp Pro Asp Gly Pro Val Leu
290 295 300
Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Thr Val Leu Ser Lys Asp
305 310 315 320
Pro Asn Glu Leu Tyr Ser Asp Leu Phe Ser Lys Asn Leu Val Thr Glu
325 330 335
Tyr Glu Leu Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr Ala
340 345 350
Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys Glu Phe Tyr Ile
355 360 365
Glu Lys Asp Asp Ser Asp Ala Leu Lys Ala Leu Phe
370 375 380
<210> 34
<211> 1149
<212> DNA
<213> 人工序列
<400> 34
atgtacatcg agaaagacga tagcgacgca ctgaaagcac tgttcgctag caaaggtgaa 60
gaactgttta ccggtgttgt tccgattctg gttgaactgg atggtgatgt taatggccac 120
aaattttcag ttcgtggtga aggcgaaggt gatgcaacca ttggtaaact gaccctgaaa 180
tttatctgta ccaccggtaa gcttccagtt ccgtggccga ccctggttac caccctgacc 240
tatggtgttc agtgttttgc acgttatccg gatcacatga aacgccacga ttttttcaaa 300
agcgcaatgc cggaaggtta tgttcaagaa cgtaccatta gctttaaaga cgtcggcaat 360
tttatggttc tgagcgttga tgacgtcgac ggtaaataca aaacccgtgc agttgttaaa 420
tttgaaggta ccggtaactt tatggtgctg tcagttgatg atggtaccga taccctggtg 480
aatcgtattg ttctgaaagg caccgatttt aaagaagatg gcaacattct taagaccagc 540
cgtccgatgg ttgatctgac ctttggtggt gtgcagctta agggtcataa actggaatat 600
aatttcaaca gccacaacgt gtatatcacc gcggacaaaa cctcacgtcc tatggtggac 660
ctgacattcg gtggcgttca gaccgcggac aaacagaaaa atggtattaa agccaatttt 720
accgtgcggc ataatgttga ggacggatcc atttttaacg atgttccgca gcgtaccacc 780
agtacctttg atccgggatc cgttcagctg gcagatcatt atcagcagaa taccccgatt 840
ggtgacggtc cgatctttaa tgatgtgcct cagcgcacaa cctcaacctt cgatccggac 900
ggtccggttc tgctgccgga taatcattat ctgagcaccc agaccgttct gagcaaagat 960
ccgaatgagc tctatagcga cctgtttagc aaaaatctgg ttaccgaata tgagctcaaa 1020
cgtgatcaca tggtgctgct ggaatttgtt accgcagcag gtattaccct gggtatggat 1080
gaactgtata aagaattcta tatcgaaaaa gatgattccg atgccctgaa agccctgttt 1140
taactcgag 1149
<210> 35
<211> 14
<212> PRT
<213> 人工序列
<400> 35
Tyr Ile Glu Lys Asp Asp Ser Asp Ala Leu Lys Ala Leu Phe
1 5 10
<210> 36
<211> 10
<212> PRT
<213> 人工序列
<400> 36
Gly Asn Phe Met Val Leu Ser Val Asp Asp
1 5 10
<210> 37
<211> 15
<212> PRT
<213> 人工序列
<400> 37
Lys Thr Ser Arg Pro Met Val Asp Leu Thr Phe Gly Gly Val Gln
1 5 10 15
<210> 38
<211> 15
<212> PRT
<213> 人工序列
<400> 38
Ile Phe Asn Asp Val Pro Gln Arg Thr Thr Ser Thr Phe Asp Pro
1 5 10 15
<210> 39
<211> 14
<212> PRT
<213> 人工序列
<400> 39
Leu Tyr Ser Asp Leu Phe Ser Lys Asn Leu Val Thr Glu Tyr
1 5 10
<210> 40
<211> 14
<212> PRT
<213> 人工序列
<400> 40
Tyr Ile Glu Lys Asp Asp Ser Asp Ala Leu Lys Ala Leu Phe
1 5 10
<210> 41
<211> 10
<212> PRT
<213> 人工序列
<400> 41
Lys Leu Ser Ala Thr Asp Trp Ser Ala Ile
1 5 10
<210> 42
<211> 8
<212> PRT
<213> 人工序列
<400> 42
Lys Pro Lys Pro Gln Pro Glu Lys
1 5
<210> 43
<211> 9
<212> PRT
<213> 人工序列
<400> 43
Lys Lys Met Thr Pro Ser Asp Gln Ile
1 5
<210> 44
<211> 10
<212> PRT
<213> 人工序列
<400> 44
Val Glu Leu Pro Trp Pro Leu Glu Thr Ile
1 5 10
<210> 45
<211> 340
<212> PRT
<213> 人工序列
<400> 45
Met Lys Leu Ser Ala Thr Asp Trp Ser Ala Ile Lys Gly Glu Glu Leu
1 5 10 15
Phe Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn
20 25 30
Gly His Lys Phe Ser Val Arg Gly Glu Gly Glu Gly Asp Ala Thr Ile
35 40 45
Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val
50 55 60
Pro Trp Pro Thr Leu Val Thr Thr Leu Thr Tyr Gly Val Gln Cys Phe
65 70 75 80
Ala Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala
85 90 95
Met Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Val
100 105 110
Lys Pro Lys Pro Gln Pro Glu Lys Asp Val Asp Gly Lys Tyr Lys Thr
115 120 125
Arg Ala Val Val Lys Phe Glu Gly Thr Lys Lys Met Thr Pro Ser Asp
130 135 140
Gln Ile Gly Thr Asp Thr Leu Val Asn Arg Ile Val Leu Lys Gly Thr
145 150 155 160
Asp Phe Lys Glu Asp Gly Asn Ile Leu Lys Val Glu Leu Pro Trp Pro
165 170 175
Leu Glu Thr Ile Leu Lys Gly His Lys Leu Glu Tyr Asn Phe Asn Ser
180 185 190
His Asn Val Tyr Ile Thr Ala Asp Lys Pro Lys Pro Gln Pro Glu Lys
195 200 205
Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe Thr Val Arg
210 215 220
His Asn Val Glu Asp Gly Ser Lys Leu Ser Ala Thr Asp Trp Ser Ala
225 230 235 240
Ile Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile
245 250 255
Gly Asp Gly Pro Val Glu Leu Pro Trp Pro Leu Glu Thr Ile Asp Gly
260 265 270
Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Thr Val Leu
275 280 285
Ser Lys Asp Pro Asn Glu Leu Lys Lys Met Thr Pro Ser Asp Gln Ile
290 295 300
Glu Leu Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr Ala Ala
305 310 315 320
Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys Leu Ser Ala Thr Asp
325 330 335
Trp Ser Ala Ile
340
<210> 46
<211> 1023
<212> DNA
<213> 人工序列
<400> 46
atgaaactga gcgcaaccga ttggagcgca attaaaggtg aagaactgtt taccggtgtt 60
gttccgattc tggttgaact ggatggtgat gttaatggcc acaaattttc agttcgtggt 120
gaaggcgaag gtgatgcaac cattggtaaa ctgaccctga aatttatctg taccaccggt 180
aagcttccag ttccgtggcc gaccctggtt accaccctga cctatggtgt tcagtgtttt 240
gcacgttatc cggatcacat gaaacgccac gattttttca aaagcgcaat gccggaaggt 300
tatgttcaag aacgtaccat tagcttcaaa gacgtcaaac cgaaaccgca gccggaaaaa 360
gacgtcgatg gtaaatacaa aacccgtgcc gttgttaaat ttgaaggtac caaaaaaatg 420
accccgagcg atcagattgg taccgatacc ctggtgaatc gtattgttct gaaaggcacc 480
gattttaaag aagatggcaa catccttaag gtggaactgc cgtggcctct ggaaaccatt 540
cttaagggtc ataaactgga atataatttc aacagccaca acgtgtatat caccgcggac 600
aaacctaaac ctcaacctga aaaaaccgcg gacaaacaga aaaatggcat caaagcaaat 660
tttaccgtgc gccataatgt tgaggatgga tccaaactgt cagccaccga ttggtcagca 720
attggatccg ttcagctggc agatcattat cagcagaata ccccgattgg tgacggtccg 780
gttgagctgc cttggccact ggaaacaatt gacggtccgg tgctgctgcc ggataatcat 840
tatctgagca cccagaccgt tctgagcaaa gatccgaatg agctcaaaaa aatgacaccg 900
tcagatcaga tcgagctcaa acgtgatcac atggttctgc tggaatttgt taccgcagca 960
ggtattaccc tgggtatgga tgaactgtat aaactgagtg cgacagactg gtctgcaatc 1020
taa 1023
<210> 47
<211> 9
<212> PRT
<213> 人工序列
<400> 47
His Arg Ile Arg Leu Leu Leu Gln Ser
1 5
<210> 48
<211> 9
<212> PRT
<213> 人工序列
<400> 48
Ser Tyr Arg Thr Gly Ala Glu Arg Val
1 5
<210> 49
<211> 9
<212> PRT
<213> 人工序列
<400> 49
Asn Gly Val Lys Gln Thr Val Asp Val
1 5
<210> 50
<211> 9
<212> PRT
<213> 人工序列
<400> 50
Gln Ser Arg Thr Leu Asp Ser Arg Asp
1 5
<210> 51
<211> 338
<212> PRT
<213> 人工序列
<400> 51
Met His Arg Ile Arg Leu Leu Leu Gln Ser Lys Gly Glu Glu Leu Phe
1 5 10 15
Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn Gly
20 25 30
His Lys Phe Ser Val Arg Gly Glu Gly Glu Gly Asp Ala Thr Ile Gly
35 40 45
Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val Pro
50 55 60
Trp Pro Thr Leu Val Thr Thr Leu Thr Tyr Gly Val Gln Cys Phe Ala
65 70 75 80
Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala Met
85 90 95
Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Val Ser
100 105 110
Tyr Arg Thr Gly Ala Glu Arg Val Asp Val Asp Gly Lys Tyr Lys Thr
115 120 125
Arg Ala Val Val Lys Phe Glu Gly Thr Asn Gly Val Lys Gln Thr Val
130 135 140
Asp Val Gly Thr Asp Thr Leu Val Asn Arg Ile Val Leu Lys Gly Thr
145 150 155 160
Asp Phe Lys Glu Asp Gly Asn Ile Leu Lys Gln Ser Arg Thr Leu Asp
165 170 175
Ser Arg Asp Leu Lys Gly His Lys Leu Glu Tyr Asn Phe Asn Ser His
180 185 190
Asn Val Tyr Ile Thr Ala Asp Gln Ser Arg Thr Leu Asp Ser Arg Asp
195 200 205
Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe Thr Val Arg
210 215 220
His Asn Val Glu Asp Gly Ser His Arg Ile Arg Leu Leu Leu Gln Ser
225 230 235 240
Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly
245 250 255
Asp Gly Pro Ser Tyr Arg Thr Gly Ala Glu Arg Val Asp Gly Pro Val
260 265 270
Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Thr Val Leu Ser Lys
275 280 285
Asp Pro Asn Glu Leu Asn Gly Val Lys Gln Thr Val Asp Val Glu Leu
290 295 300
Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile
305 310 315 320
Thr Leu Gly Met Asp Glu Leu Tyr Lys His Arg Ile Arg Leu Leu Leu
325 330 335
Gln Ser
<210> 52
<211> 1017
<212> DNA
<213> 人工序列
<400> 52
atgcatcgta ttcgtctgct gctgcagagc aaaggtgaag aactgtttac cggtgttgtt 60
ccgattctgg ttgaactgga tggtgatgtt aatggccaca aattttcagt tcgtggtgaa 120
ggcgaaggtg atgcaaccat tggtaaactg accctgaaat ttatctgtac caccggtaag 180
cttccagttc cgtggccgac cctggttacc accctgacct atggtgttca gtgttttgca 240
cgttatccgg atcacatgaa acgccacgat tttttcaaaa gcgcaatgcc ggaaggttat 300
gttcaagaac gtaccattag ctttaaagac gtcagctatc gtaccggtgc agaacgtgtt 360
gacgtcgatg gtaaatacaa aacccgtgcc gttgttaaat ttgaaggtac caatggcgtt 420
aaacagaccg ttgatgttgg taccgatacc ctggtgaatc gtattgttct gaaaggcacc 480
gattttaaag aagatggcaa cattcttaag cagagccgta ccctggatag ccgtgatctt 540
aagggtcata aactggaata taatttcaac agccacaacg tgtatattac cgcggaccag 600
tcacgcaccc tggattcacg tgacaccgcg gacaaacaga aaaatggtat taaagccaat 660
tttaccgtgc ggcataatgt tgaagatgga tcccatcgta tccgcctgct gctgcaaagc 720
ggatccgttc agctggcaga tcattatcag cagaataccc cgattggtga cggtccgagt 780
tatcgcacag gtgccgaacg cgtggacggt ccggttctgc tgccggataa tcattatctg 840
agcacccaga ccgttctgag caaagatccg aatgagctca atggtgtgaa acaaacagtg 900
gatgtagagc tcaaacgtga tcacatggtg ctgctggaat ttgttaccgc agcaggtatt 960
accctgggta tggatgaact gtataaacac cgcattcggc tgctgctgca atcataa 1017
<210> 53
<211> 14
<212> PRT
<213> 人工序列
<400> 53
Pro Tyr Thr Ser Arg Arg Ser Val Ala Ser Ile Val Gly Thr
1 5 10
<210> 54
<211> 10
<212> PRT
<213> 人工序列
<400> 54
Gln Tyr Tyr Asp Tyr Glu Asp Ala Thr Phe
1 5 10
<210> 55
<211> 10
<212> PRT
<213> 人工序列
<400> 55
Gly Pro Lys Gln Leu Thr Phe Glu Gly Lys
1 5 10
<210> 56
<211> 10
<212> PRT
<213> 人工序列
<400> 56
Asp Ala Thr Phe Glu Thr Tyr Ala Leu Thr
1 5 10
<210> 57
<211> 9
<212> PRT
<213> 人工序列
<400> 57
Leu Thr Val Glu Asp Ser Pro Tyr Pro
1 5
<210> 58
<211> 9
<212> PRT
<213> 人工序列
<400> 58
Ala Leu Ala Thr Tyr Gln Ser Glu Tyr
1 5
<210> 59
<211> 14
<212> PRT
<213> 人工序列
<400> 59
Pro Gly Ile Val Ile Pro Pro Lys Ala Leu Phe Thr Gln Gln
1 5 10
<210> 60
<211> 9
<212> PRT
<213> 人工序列
<400> 60
Ala Val Glu Ala Glu Arg Ala Gly Arg
1 5
<210> 61
<211> 9
<212> PRT
<213> 人工序列
<400> 61
Thr Thr Thr Glu Tyr Ser Asn Ala Arg
1 5
<210> 62
<211> 14
<212> PRT
<213> 人工序列
<400> 62
Glu Arg Ala Gly Glu Ala Met Val Leu Val Tyr Tyr Glu Ser
1 5 10
<210> 63
<211> 1101
<212> DNA
<213> 人工序列
<400> 63
atgccctaca cctcacgtcg cagcgtagct tcgattgttg gcacgtctta ttggaaaggg 60
tctcaatact atgactatga agatgcaact tttaaaggag aggagttgtt taccggcgtg 120
gtgccgatcc ttgtggagtt ggatggagac gttaacggtc acaagttttc agttcgcggt 180
gaaggcgaag gcgacgcgac tattggtaag cttaccttga agttcatctg tactacgggg 240
cctaagcagc ttacgttcga ggggaaatta cctgtcccct ggccaacatt ggtcacgaca 300
ttaacctatg gcgtgcagtg ttttgcgcgt taccccgatc acatgaagcg tcacgacttc 360
tttaagtccg cgatgccgga agggtatgtc caggaacgca cgatttcgtt caaagacgcg 420
acctttgaga cttacgcatt aaccgggggc tcgggcgagg cagccgcaaa agaagctgct 480
gctgacggca aatacaaaac tcgtgcggtc gtaaaattcg agggagacac tttagttaat 540
cgtattgtgc tgaaagggac tgacttcaag gaagatggaa acattttgac ggttgaggat 600
agcccctatc ctggccataa acttgagtac aacttcaatt cacataatgt ctacattaca 660
gcacttgcaa cgtatcagtc tgagtacgat aagcagaaga atggtatcaa ggctaatttt 720
acggtccgtc ataatgttga ggatgggagc gtgcagttag ctgaccatta tcaacaaaat 780
acgcccattg gggaccccgg catcgtgatt cccccaaaag cattattcac ccagcaagtg 840
cttttaccag acaaccatta cttgagcacc caaacggtgt taagcaagga ccccaatgag 900
aaagcagtgg aggcggaacg cgctggacgt gatcatatgg tacttcttga attcgtaacg 960
gcggccggga tcactttggg aatggacgag ttatataaag agcgtgcggg tgaggccatg 1020
gtgcttgtgt attacgagtc agaagccgcg aaggaggctg ccaagacaac aacggaatac 1080
agtaacgccc gtaaaaagta a 1101
<210> 64
<211> 366
<212> PRT
<213> 人工序列
<400> 64
Met Pro Tyr Thr Ser Arg Arg Ser Val Ala Ser Ile Val Gly Thr Ser
1 5 10 15
Tyr Trp Lys Gly Ser Gln Tyr Tyr Asp Tyr Glu Asp Ala Thr Phe Lys
20 25 30
Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp
35 40 45
Gly Asp Val Asn Gly His Lys Phe Ser Val Arg Gly Glu Gly Glu Gly
50 55 60
Asp Ala Thr Ile Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly
65 70 75 80
Pro Lys Gln Leu Thr Phe Glu Gly Lys Leu Pro Val Pro Trp Pro Thr
85 90 95
Leu Val Thr Thr Leu Thr Tyr Gly Val Gln Cys Phe Ala Arg Tyr Pro
100 105 110
Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly
115 120 125
Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Ala Thr Phe Glu Thr
130 135 140
Tyr Ala Leu Thr Gly Gly Ser Gly Glu Ala Ala Ala Lys Glu Ala Ala
145 150 155 160
Ala Asp Gly Lys Tyr Lys Thr Arg Ala Val Val Lys Phe Glu Gly Asp
165 170 175
Thr Leu Val Asn Arg Ile Val Leu Lys Gly Thr Asp Phe Lys Glu Asp
180 185 190
Gly Asn Ile Leu Thr Val Glu Asp Ser Pro Tyr Pro Gly His Lys Leu
195 200 205
Glu Tyr Asn Phe Asn Ser His Asn Val Tyr Ile Thr Ala Leu Ala Thr
210 215 220
Tyr Gln Ser Glu Tyr Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe
225 230 235 240
Thr Val Arg His Asn Val Glu Asp Gly Ser Val Gln Leu Ala Asp His
245 250 255
Tyr Gln Gln Asn Thr Pro Ile Gly Asp Pro Gly Ile Val Ile Pro Pro
260 265 270
Lys Ala Leu Phe Thr Gln Gln Val Leu Leu Pro Asp Asn His Tyr Leu
275 280 285
Ser Thr Gln Thr Val Leu Ser Lys Asp Pro Asn Glu Lys Ala Val Glu
290 295 300
Ala Glu Arg Ala Gly Arg Asp His Met Val Leu Leu Glu Phe Val Thr
305 310 315 320
Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys Glu Arg Ala
325 330 335
Gly Glu Ala Met Val Leu Val Tyr Tyr Glu Ser Glu Ala Ala Lys Glu
340 345 350
Ala Ala Lys Thr Thr Thr Glu Tyr Ser Asn Ala Arg Lys Lys
355 360 365
<210> 65
<211> 14
<212> PRT
<213> 人工序列
<400> 65
Ser Pro Trp Ser Trp Pro Asp Leu Asp Leu Lys Pro Gly Ala
1 5 10
<210> 66
<211> 14
<212> PRT
<213> 人工序列
<400> 66
Asp Gly Asn Cys Asp Gly Arg Gly Lys Ser Thr Arg Ser Thr
1 5 10
<210> 67
<211> 14
<212> PRT
<213> 人工序列
<400> 67
Val Phe Ser Pro Gly Arg Lys Asn Gly Ser Phe Ile Ile Asp
1 5 10
<210> 68
<211> 14
<212> PRT
<213> 人工序列
<400> 68
His Val Gln Asp Cys Asp Glu Ser Val Leu Thr Arg Leu Glu
1 5 10
<210> 69
<211> 14
<212> PRT
<213> 人工序列
<400> 69
Asp Cys Asp Gly Ser Ile Leu Gly Ala Ala Val Asn Gly Lys
1 5 10
<210> 70
<211> 9
<212> PRT
<213> 人工序列
<400> 70
Phe Thr Thr Arg Val Tyr Met Asp Ala
1 5
<210> 71
<211> 14
<212> PRT
<213> 人工序列
<400> 71
Arg Asp Ser Asp Asp Trp Leu Asn Lys Tyr Ser Tyr Tyr Pro
1 5 10
<210> 72
<211> 14
<212> PRT
<213> 人工序列
<400> 72
Glu Ser Glu Met Phe Met Pro Arg Ser Ile Gly Gly Pro Val
1 5 10
<210> 73
<211> 14
<212> PRT
<213> 人工序列
<400> 73
Ala Glu Ala Glu Met Val Ile His His Gln His Val Gln Asp
1 5 10
<210> 74
<211> 19
<212> PRT
<213> 人工序列
<400> 74
Leu Glu His Glu Met Trp Arg Ser Arg Ala Asp Glu Ile Asn Ala Ile
1 5 10 15
Phe Glu Glu
<210> 75
<211> 430
<212> PRT
<213> 人工序列
<400> 75
Met Gly Ser Ser His His His His His His Ser Ser Gly Leu Val Pro
1 5 10 15
Arg Gly Ser His Met Ser Pro Trp Ser Trp Pro Asp Leu Asp Leu Lys
20 25 30
Pro Gly Ala Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu
35 40 45
Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Arg Gly
50 55 60
Glu Gly Glu Gly Asp Ala Thr Ile Gly Lys Leu Thr Leu Lys Phe Ile
65 70 75 80
Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr
85 90 95
Leu Thr Tyr Gly Val Gln Cys Phe Ala Arg Tyr Pro Asp His Met Lys
100 105 110
Arg His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu
115 120 125
Arg Thr Ile Ser Phe Lys Asp Gly Asn Cys Asp Gly Arg Gly Lys Ser
130 135 140
Thr Arg Ser Thr Gly Gly Ser Gly Glu Ala Ala Ala Lys Glu Ala Ala
145 150 155 160
Ala Lys Lys Tyr Lys Thr Arg Ala Val Val Lys Phe Glu Gly Val Phe
165 170 175
Ser Pro Gly Arg Lys Asn Gly Ser Phe Ile Ile Asp Gly Gly Ser Gly
180 185 190
Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Asp Thr Leu Val Asn Arg
195 200 205
Ile Val Leu Lys Gly Thr Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly
210 215 220
His Lys His Val Gln Asp Cys Asp Glu Ser Val Leu Thr Arg Leu Glu
225 230 235 240
Tyr Asn Phe Asn Ser His Asn Val Tyr Ile Thr Ala Asp Cys Asp Gly
245 250 255
Ser Ile Leu Gly Ala Ala Val Asn Gly Lys Gln Lys Asn Gly Ile Lys
260 265 270
Ala Asn Phe Thr Val Arg His Asn Val Glu Asp Phe Thr Thr Arg Val
275 280 285
Tyr Met Asp Ala Gly Thr Ser Trp Lys Gly Gly Ser Val Gln Leu Ala
290 295 300
Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Arg Asp Ser Asp Asp
305 310 315 320
Trp Leu Asn Lys Tyr Ser Tyr Tyr Pro Val Leu Leu Pro Asp Asn His
325 330 335
Tyr Leu Ser Thr Gln Thr Val Leu Ser Lys Asp Pro Asn Glu Ser Glu
340 345 350
Met Phe Met Pro Arg Ser Ile Gly Gly Pro Val Lys Arg Asp His Met
355 360 365
Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp
370 375 380
Glu Leu Tyr Lys Leu Glu His Glu Met Trp Arg Ser Arg Ala Asp Glu
385 390 395 400
Ile Asn Ala Ile Phe Glu Glu Thr Ser Tyr Trp Lys Gly Ser Ala Glu
405 410 415
Ala Glu Met Val Ile His His Gln His Val Gln Asp Lys Lys
420 425 430
<210> 76
<211> 1293
<212> DNA
<213> 人工序列
<400> 76
atgggcagca gccatcatca tcatcatcac agcagcggcc tggtgccgcg cggcagccat 60
atgtccccat ggagttggcc tgaccttgat ttaaagcccg gtgctaaagg agaagaactg 120
ttcacagggg tcgttcccat cttagtggag ctggacggcg acgtgaacgg ccataaattc 180
agtgtgcgcg gggaaggaga aggggacgca acgattggta agttgacgct gaaatttatc 240
tgtacaactg gtaagcttcc agtgccgtgg ccgacgcttg tgacgacact tacttatgga 300
gtccagtgtt ttgcgcgtta tccagatcac atgaaacgcc acgacttctt taagtccgca 360
atgccggagg gctacgtgca ggaacgcaca atctcgttta aggacgggaa ctgcgatggc 420
cgtgggaaaa gtacacgctc aacgggcgga tcaggcgaag ccgcagcaaa agaggctgcg 480
gccaaaaaat ataaaactcg tgccgtagtg aaatttgagg gagtgttttc cccgggccgt 540
aagaacggca gttttatcat tgacggcggc tcaggagaag cggctgcaaa ggaggccgcc 600
gcgaaggaca ccttagtgaa ccgcattgtt ttgaaaggaa cggattttaa agaggacgga 660
aacattttag gacacaagca tgtccaagac tgcgatgaga gtgttcttac gcgtttagaa 720
tataatttca atagtcataa cgtatacatt acggctgatt gtgatggcag tatcttagga 780
gcggctgtta acgggaagca aaagaatgga atcaaagcca actttactgt tcgtcataat 840
gtcgaagact tcaccactcg tgtctacatg gatgccggta ctagctggaa aggcgggtcc 900
gttcagcttg cggatcatta ccaacaaaac actccgatcg gggaccgtga ctccgatgat 960
tggctgaaca agtattcata ctaccctgtg ctgctgcccg ataaccatta tttgagcaca 1020
cagaccgtgc tgtctaaaga tcctaatgaa tcagaaatgt ttatgcctcg ttcgatcggg 1080
ggacccgtta aacgcgatca catggtattg ttggaattcg ttacggcagc gggcatcacg 1140
cttggtatgg atgagttgta taaacttgag catgaaatgt ggcgctcgcg tgcagacgaa 1200
atcaatgcaa tttttgaaga gactagctat tggaagggta gtgcggaagc tgaaatggtc 1260
attcaccacc agcatgtcca ggacaaaaaa taa 1293
<210> 77
<211> 245
<212> PRT
<213> 人工序列
<400> 77
Met Gly Ala His Ala Ser Val Ile Lys Pro Glu Met Lys Ile Lys Leu
1 5 10 15
Arg Met Glu Gly Ala Val Asn Gly His Lys Phe Val Ile Glu Gly Glu
20 25 30
Gly Ile Gly Lys Pro Tyr Glu Gly Thr Gln Thr Leu Asp Leu Thr Val
35 40 45
Glu Glu Gly Ala Pro Leu Pro Phe Ser Tyr Asp Ile Leu Thr Pro Ala
50 55 60
Phe Gln Tyr Gly Asn Arg Ala Phe Thr Lys Tyr Pro Glu Asp Ile Pro
65 70 75 80
Asp Tyr Phe Lys Gln Ala Phe Pro Glu Gly Tyr Ser Trp Glu Arg Ser
85 90 95
Met Thr Tyr Glu Asp Gln Gly Ile Cys Ile Ala Thr Ser Asp Ile Thr
100 105 110
Met Glu Gly Asp Cys Phe Phe Tyr Glu Ile Arg Phe Asp Gly Thr Asn
115 120 125
Phe Pro Pro Asn Gly Pro Val Met Gln Lys Lys Thr Leu Lys Trp Glu
130 135 140
Pro Ser Thr Glu Lys Met Tyr Val Glu Asp Gly Val Leu Lys Gly Asp
145 150 155 160
Val Glu Met Ala Leu Leu Leu Glu Gly Gly Gly His Tyr Arg Cys Asp
165 170 175
Phe Lys Thr Thr Tyr Lys Ala Lys Lys Asp Val Arg Leu Pro Asp Ala
180 185 190
His Glu Val Asp His Arg Ile Glu Ile Leu Ser His Asp Lys Asp Tyr
195 200 205
Asn Lys Val Arg Leu Tyr Glu His Ala Glu Ala Arg Tyr Ser Gly Gly
210 215 220
Gly Ser Gly Gly Gly Ala Ser Gly Lys Pro Ile Pro Asn Pro Leu Leu
225 230 235 240
Gly Leu Asp Ser Thr
245
<210> 78
<211> 738
<212> DNA
<213> 人工序列
<400> 78
atgggtgcgc acgcgtctgt tatcaaaccg gaaatgaaaa tcaaactgcg tatggaaggt 60
gcggttaacg gtcacaaatt cgttatcgaa ggtgaaggta tcggtaaacc gtacgaaggt 120
acccagaccc tggacctgac cgttgaagaa ggtgcgccgc tgccgttctc ttacgacatc 180
ctgaccccgg cgttccagta cggtaaccgt gcgttcacca aatacccgga agacatcccg 240
gactacttca aacaggcgtt cccggaaggt tactcttggg aacgttctat gacctacgaa 300
gaccagggta tctgcatcgc gacctctgac atcaccatgg aaggtgactg cttcttctac 360
gaaatccgtt tcgacggtac caacttcccg ccgaacggtc cggttatgca gaaaaaaacc 420
ctgaaatggg aaccgtctac cgaaaaaatg tacgttgaag acggtgttct gaaaggtgac 480
gttgaaatgg cgctgctgct ggaaggtggt ggtcactacc gttgcgactt caaaaccacc 540
tacaaagcga aaaaagacgt tcgtctgccg gacgcgcacg aagttgacca ccgtatcgaa 600
atcctgtctc acgacaaaga ctacaacaaa gttcgtctgt acgaacacgc ggaagcgcgt 660
tactctggtg gtggttctgg tggtggtgcg tctggtaaac cgatcccgaa cccgctgctg 720
ggtctggact ctacctaa 738
<210> 79
<211> 20
<212> PRT
<213> 人工序列
<400> 79
Asp Leu Arg Gln Met Arg Thr Val Thr Pro Ile Arg Met Gln Gly Gly
1 5 10 15
Cys Gly Ser Cys
20
<210> 80
<211> 20
<212> PRT
<213> 人工序列
<400> 80
Gly Cys Gly Ser Cys Trp Ala Phe Ser Gly Val Ala Ala Thr Glu Ser
1 5 10 15
Ala Tyr Leu Ala
20
<210> 81
<211> 15
<212> PRT
<213> 人工序列
<400> 81
Gln Glu Ser Tyr Tyr Arg Tyr Val Ala Arg Glu Gln Ser Cys Arg
1 5 10 15
<210> 82
<211> 15
<212> PRT
<213> 人工序列
<400> 82
His Ala Val Asn Ile Val Gly Tyr Ser Asn Ala Gln Gly Val Asp
1 5 10 15
<210> 83
<211> 20
<212> PRT
<213> 人工序列
<400> 83
Cys His Gly Ser Glu Pro Cys Ile Ile His Arg Gly Lys Pro Phe Gln
1 5 10 15
Leu Glu Ala Val
20
<210> 84
<211> 20
<212> PRT
<213> 人工序列
<400> 84
Tyr Asp Ile Lys Tyr Thr Trp Asn Val Pro Lys Ile Ala Pro Lys Ser
1 5 10 15
Glu Asn Val Val
20
<210> 85
<211> 15
<212> PRT
<213> 人工序列
<400> 85
Asn Thr Lys Thr Ala Lys Ile Glu Ile Lys Ala Ser Ile Asp Gly
1 5 10 15
<210> 86
<211> 15
<212> PRT
<213> 人工序列
<400> 86
Gly Val Leu Ala Cys Ala Ile Ala Thr His Ala Lys Ile Arg Asp
1 5 10 15
<210> 87
<211> 20
<212> PRT
<213> 人工序列
<400> 87
Pro Lys Asp Pro His Lys Phe Tyr Ile Cys Ser Asn Trp Glu Ala Val
1 5 10 15
His Lys Asp Cys
20
<210> 88
<211> 366
<212> PRT
<213> 人工序列
<400> 88
Met Pro Lys Asp Pro His Lys Phe Tyr Ile Cys Ser Asn Trp Glu Ala
1 5 10 15
Val His Lys Asp Cys Ser Val Ile Lys Pro Glu Met Lys Ile Lys Leu
20 25 30
Arg Met Glu Gly Ala Val His Ala Val Asn Ile Val Gly Tyr Ser Asn
35 40 45
Ala Gln Gly Val Asp His Lys Phe Val Ile Glu Gly Glu Gly Ile Gly
50 55 60
Lys Pro Tyr Glu Gly Thr Gln Thr Leu Asp Leu Thr Val Glu Glu Gly
65 70 75 80
Ala Pro Leu Pro Phe Ser Tyr Asp Ile Leu Thr Pro Ala Phe Gln Tyr
85 90 95
Gly Asn Arg Ala Phe Thr Lys Tyr Pro Glu Asp Ile Pro Asp Tyr Phe
100 105 110
Lys Gln Ala Phe Pro Glu Gly Tyr Ser Trp Glu Arg Ser Met Thr Tyr
115 120 125
Gly Val Leu Ala Cys Ala Ile Ala Thr His Ala Lys Ile Arg Asp Gly
130 135 140
Ile Cys Ile Ala Thr Ser Asp Ile Thr Met Glu Tyr Asp Ile Lys Tyr
145 150 155 160
Thr Trp Asn Val Pro Lys Ile Ala Pro Lys Ser Glu Asn Val Val Cys
165 170 175
Phe Phe Tyr Glu Ile Arg Phe Asp Gly Thr Gln Glu Ser Tyr Tyr Arg
180 185 190
Tyr Val Ala Arg Glu Gln Ser Cys Arg Thr Leu Lys Trp Glu Pro Ser
195 200 205
Thr Glu Lys Met Tyr Val Glu Asp Gly Val Leu Lys Gly Asp Val Glu
210 215 220
Met Ala Leu Leu Leu Cys His Gly Ser Glu Pro Cys Ile Ile His Arg
225 230 235 240
Gly Lys Pro Phe Gln Leu Glu Ala Val His Tyr Arg Cys Asp Phe Lys
245 250 255
Thr Thr Tyr Lys Ala Gly Cys Gly Ser Cys Trp Ala Phe Ser Gly Val
260 265 270
Ala Ala Thr Glu Ser Ala Tyr Leu Ala His Glu Val Asp His Arg Ile
275 280 285
Glu Ile Leu Ser His Asp Lys Asp Tyr Asn Lys Val Arg Leu Tyr Glu
290 295 300
His Ala Glu Ala Arg Tyr Ser Gly Gly Ser Gly Asp Leu Arg Gln Met
305 310 315 320
Arg Thr Val Thr Pro Ile Arg Met Gln Gly Gly Cys Gly Ser Cys Gly
325 330 335
Gly Ser Gly Asn Thr Lys Thr Ala Lys Ile Glu Ile Lys Ala Ser Ile
340 345 350
Asp Gly Leu Asp Ser Thr His His His His His His Lys Lys
355 360 365
<210> 89
<211> 1101
<212> DNA
<213> 人工序列
<400> 89
atgccgaaag atccccacaa gttctatatt tgctcaaact gggaggccgt gcacaaagat 60
tgttctgtta tcaagccaga gatgaaaatc aaactgcgca tggagggggc tgtccatgcg 120
gtaaacattg tgggttactc aaatgcgcag ggagtggacc ataagtttgt catcgaaggc 180
gagggcatcg gtaaacctta tgaaggcact cagactttgg atttaacggt cgaagaagga 240
gcgcctttgc cattttcgta tgatatctta accccggcgt ttcaatacgg aaatcgcgcg 300
ttcacaaagt atcccgaaga catccccgat tacttcaagc aagcttttcc agaaggctac 360
agctgggagc gttcaatgac gtatggagtc cttgcatgtg ctatcgccac acatgctaaa 420
atccgcgatg gtatttgtat tgccacgtca gatatcacaa tggaatacga tatcaagtac 480
acttggaacg tgccaaaaat cgctcccaag tcagaaaacg tggtgtgttt cttctatgag 540
attcgttttg atggtaccca agagtcttat tatcgttatg ttgcacgtga acaaagttgt 600
cgtacgttga agtgggagcc ttctacagaa aaaatgtatg tggaggacgg cgtgcttaaa 660
ggagacgtgg agatggcact gcttttgtgt catgggtccg aaccgtgtat tattcatcgc 720
ggaaaaccct ttcaattgga agcggtccac taccgctgcg attttaagac cacatataaa 780
gctggatgcg gttcctgctg ggcgttctcc ggtgtagctg ccactgaatc ggcttacttg 840
gcgcacgaag tcgatcatcg tatcgagatt ttatcgcacg acaaggatta caacaaagtc 900
cgcttatatg agcacgcaga agcacgctac tctggtggca gtggtgactt acgtcagatg 960
cgtacagtga cacctattcg tatgcaagga ggatgtggta gctgtggagg atcaggcaac 1020
accaagacgg cgaaaattga aattaaagca tccattgatg gacttgattc gacgcaccac 1080
caccatcatc acaaaaagta g 1101
<210> 90
<211> 333
<212> PRT
<213> 人工序列
<400> 90
Met Gly Ala His Ala Ser Val Ile Lys Phe Ala Glu Leu Leu Glu Gln
1 5 10 15
Gln Lys Asn Ala Gln Phe Pro Gly Lys Pro Glu Met Lys Ile Lys Leu
20 25 30
Arg Met Glu Gly Ala Val Asn Gly His Lys Phe Val Ile Glu Gly Glu
35 40 45
Gly Ile Gly Lys Pro Tyr Glu Gly Thr Gln Thr Leu Asp Leu Thr Val
50 55 60
Glu Glu Asp Ser Ser Ala His Ser Thr Pro Ser Thr Pro Ala Tyr Asp
65 70 75 80
Ile Leu Thr Pro Ala Phe Gln Tyr Gly Asn Arg Ala Phe Thr Lys Tyr
85 90 95
Pro Glu Asp Ile Pro Asp Tyr Phe Lys Gln Ala Phe Pro Glu Gly Tyr
100 105 110
Ser Trp Glu Arg Ser Met Thr Tyr Glu Asp Gln Gly Ile Cys Ile Ala
115 120 125
Thr Ser Asp Ile Thr Met Glu Gly Asp Lys Pro Ser Pro Phe Gly Gln
130 135 140
Ala Ala Ala Ala Asp Lys Cys Phe Phe Tyr Glu Ile Arg Phe Asp Gly
145 150 155 160
Thr Phe Gly Gln Ala Ala Ala Gly Asp Lys Pro Ser Thr Leu Lys Trp
165 170 175
Glu Pro Ser Thr Glu Lys Met Tyr Val Glu Ala Glu Pro Lys Pro Ala
180 185 190
Glu Pro Lys Ser Val Leu Lys Gly Asp Val Glu Met Ala Leu Leu Leu
195 200 205
Thr Ser Ser Thr Pro Pro Ser Gly Thr Glu Asn Lys Pro Ala Thr Gly
210 215 220
His Tyr Arg Cys Asp Phe Lys Thr Thr Tyr Lys Ala Gly Thr Ser Glu
225 230 235 240
Glu Gly Ser Arg Gly Gly Ser Ser Met Pro Ser His Glu Val Asp His
245 250 255
Arg Ile Glu Ile Leu Ser His Ser Pro Phe Gly Gln Ala Ala Ala Gly
260 265 270
Asp Lys Lys Val Arg Leu Tyr Glu His Ala Glu Ala Arg Tyr Ser Gly
275 280 285
Gly Gly Ser Gly Lys Ala Ala Ile Ala Pro Ala Gly Gly Ala Ser Gly
290 295 300
Lys Gln Arg Ala Ala Glu Ala Thr Lys Pro Ile Pro Asn Pro Leu Leu
305 310 315 320
Gly Leu Asp Ser Thr His His His His His His Lys Lys
325 330
<210> 91
<211> 1002
<212> PRT
<213> 人工序列
<400> 91
Ala Thr Gly Gly Gly Thr Gly Cys Gly Cys Ala Cys Gly Cys Ala Ala
1 5 10 15
Gly Cys Gly Thr Gly Ala Thr Thr Ala Ala Gly Thr Thr Thr Gly Cys
20 25 30
Gly Gly Ala Ala Cys Thr Thr Thr Thr Ala Gly Ala Ala Cys Ala Gly
35 40 45
Cys Ala Gly Ala Ala Ala Ala Ala Cys Gly Cys Ala Cys Ala Gly Thr
50 55 60
Thr Cys Cys Cys Gly Gly Gly Gly Ala Ala Ala Cys Cys Cys Gly Ala
65 70 75 80
Ala Ala Thr Gly Ala Ala Ala Ala Thr Cys Ala Ala Ala Cys Thr Thr
85 90 95
Cys Gly Cys Ala Thr Gly Gly Ala Gly Gly Gly Gly Gly Cys Gly Gly
100 105 110
Thr Ala Ala Ala Cys Gly Gly Cys Cys Ala Cys Ala Ala Gly Thr Thr
115 120 125
Thr Gly Thr Thr Ala Thr Cys Gly Ala Gly Gly Gly Gly Gly Ala Ala
130 135 140
Gly Gly Thr Ala Thr Cys Gly Gly Ala Ala Ala Gly Cys Cys Thr Thr
145 150 155 160
Ala Cys Gly Ala Gly Gly Gly Ala Ala Cys Gly Cys Ala Gly Ala Cys
165 170 175
Thr Thr Thr Gly Gly Ala Cys Thr Thr Ala Ala Cys Ala Gly Thr Ala
180 185 190
Gly Ala Gly Gly Ala Ala Gly Ala Cys Thr Cys Ala Thr Cys Thr Gly
195 200 205
Cys Ala Cys Ala Thr Thr Cys Ala Ala Cys Cys Cys Cys Gly Thr Cys
210 215 220
Thr Ala Cys Thr Cys Cys Gly Gly Cys Ala Thr Ala Thr Gly Ala Thr
225 230 235 240
Ala Thr Thr Thr Thr Ala Ala Cys Thr Cys Cys Thr Gly Cys Gly Thr
245 250 255
Thr Thr Cys Ala Ala Thr Ala Thr Gly Gly Gly Ala Ala Cys Cys Gly
260 265 270
Thr Gly Cys Ala Thr Thr Thr Ala Cys Thr Ala Ala Ala Thr Ala Cys
275 280 285
Cys Cys Ala Gly Ala Gly Gly Ala Cys Ala Thr Cys Cys Cys Thr Gly
290 295 300
Ala Thr Thr Ala Thr Thr Thr Cys Ala Ala Ala Cys Ala Gly Gly Cys
305 310 315 320
Thr Thr Thr Thr Cys Cys Gly Gly Ala Ala Gly Gly Thr Thr Ala Cys
325 330 335
Thr Cys Ala Thr Gly Gly Gly Ala Gly Cys Gly Cys Thr Cys Thr Ala
340 345 350
Thr Gly Ala Cys Ala Thr Ala Thr Gly Ala Ala Gly Ala Thr Cys Ala
355 360 365
Ala Gly Gly Ala Ala Thr Cys Thr Gly Thr Ala Thr Thr Gly Cys Cys
370 375 380
Ala Cys Thr Thr Cys Gly Gly Ala Cys Ala Thr Cys Ala Cys Cys Ala
385 390 395 400
Thr Gly Gly Ala Gly Gly Gly Ala Gly Ala Cys Ala Ala Gly Cys Cys
405 410 415
Gly Ala Gly Cys Cys Cys Ala Thr Thr Thr Gly Gly Thr Cys Ala Ala
420 425 430
Gly Cys Ala Gly Cys Thr Gly Cys Cys Gly Cys Ala Gly Ala Thr Ala
435 440 445
Ala Ala Thr Gly Thr Thr Thr Thr Thr Thr Cys Thr Ala Thr Gly Ala
450 455 460
Ala Ala Thr Thr Cys Gly Thr Thr Thr Cys Gly Ala Cys Gly Gly Gly
465 470 475 480
Ala Cys Ala Thr Thr Thr Gly Gly Ala Cys Ala Ala Gly Cys Gly Gly
485 490 495
Cys Thr Gly Cys Ala Gly Gly Cys Gly Ala Cys Ala Ala Gly Cys Cys
500 505 510
Thr Ala Gly Cys Ala Cys Gly Thr Thr Gly Ala Ala Gly Thr Gly Gly
515 520 525
Gly Ala Gly Cys Cys Ala Ala Gly Cys Ala Cys Cys Gly Ala Ala Ala
530 535 540
Ala Gly Ala Thr Gly Thr Ala Cys Gly Thr Thr Gly Ala Gly Gly Cys
545 550 555 560
Thr Gly Ala Ala Cys Cys Gly Ala Ala Gly Cys Cys Ala Gly Cys Gly
565 570 575
Gly Ala Gly Cys Cys Gly Ala Ala Ala Thr Cys Ala Gly Thr Cys Thr
580 585 590
Thr Ala Ala Ala Gly Gly Gly Gly Gly Ala Thr Gly Thr Thr Gly Ala
595 600 605
Ala Ala Thr Gly Gly Cys Thr Thr Thr Gly Cys Thr Thr Cys Thr Gly
610 615 620
Ala Cys Gly Ala Gly Cys Ala Gly Cys Ala Cys Gly Cys Cys Ala Cys
625 630 635 640
Cys Ala Ala Gly Thr Gly Gly Cys Ala Cys Ala Gly Ala Ala Ala Ala
645 650 655
Cys Ala Ala Ala Cys Cys Cys Gly Cys Cys Ala Cys Ala Gly Gly Ala
660 665 670
Cys Ala Thr Thr Ala Thr Cys Gly Cys Thr Gly Cys Gly Ala Thr Thr
675 680 685
Thr Thr Ala Ala Gly Ala Cys Thr Ala Cys Ala Thr Ala Thr Ala Ala
690 695 700
Gly Gly Cys Thr Gly Gly Thr Ala Cys Cys Thr Cys Thr Gly Ala Gly
705 710 715 720
Gly Ala Gly Gly Gly Gly Thr Cys Thr Cys Gly Cys Gly Gly Ala Gly
725 730 735
Gly Thr Ala Gly Thr Ala Gly Cys Ala Thr Gly Cys Cys Gly Thr Cys
740 745 750
Ala Cys Ala Cys Gly Ala Gly Gly Thr Thr Gly Ala Cys Cys Ala Cys
755 760 765
Cys Gly Cys Ala Thr Thr Gly Ala Gly Ala Thr Cys Thr Thr Ala Thr
770 775 780
Cys Thr Cys Ala Cys Thr Cys Cys Cys Cys Thr Thr Thr Thr Gly Gly
785 790 795 800
Thr Cys Ala Gly Gly Cys Thr Gly Cys Ala Gly Cys Thr Gly Gly Gly
805 810 815
Gly Ala Thr Ala Ala Gly Ala Ala Gly Gly Thr Gly Cys Gly Thr Cys
820 825 830
Thr Thr Thr Ala Thr Gly Ala Gly Cys Ala Cys Gly Cys Gly Gly Ala
835 840 845
Gly Gly Cys Cys Cys Gly Thr Thr Ala Cys Thr Cys Thr Gly Gly Thr
850 855 860
Gly Gly Ala Gly Gly Cys Ala Gly Thr Gly Gly Gly Ala Ala Ala Gly
865 870 875 880
Cys Gly Gly Cys Ala Ala Thr Thr Gly Cys Cys Cys Cys Cys Gly Cys
885 890 895
Ala Gly Gly Cys Gly Gly Cys Gly Cys Gly Thr Cys Ala Gly Gly Gly
900 905 910
Ala Ala Ala Cys Ala Ala Cys Gly Cys Gly Cys Cys Gly Cys Thr Gly
915 920 925
Ala Gly Gly Cys Gly Ala Cys Gly Ala Ala Ala Cys Cys Gly Ala Thr
930 935 940
Cys Cys Cys Gly Ala Ala Cys Cys Cys Gly Cys Thr Gly Thr Thr Gly
945 950 955 960
Gly Gly Ala Cys Thr Thr Gly Ala Cys Ala Gly Thr Ala Cys Cys Cys
965 970 975
Ala Cys Cys Ala Thr Cys Ala Thr Cys Ala Cys Cys Ala Cys Cys Ala
980 985 990
Cys Ala Ala Gly Ala Ala Ala Thr Ala Gly
995 1000
<210> 92
<211> 12
<212> PRT
<213> 人工序列
<400> 92
Asp Ser Ser Ala His Ser Thr Pro Ser Thr Pro Ala
1 5 10
<210> 93
<211> 11
<212> PRT
<213> 人工序列
<400> 93
Phe Gly Gln Ala Ala Ala Gly Asp Lys Pro Ser
1 5 10
<210> 94
<211> 16
<212> PRT
<213> 人工序列
<400> 94
Thr Ser Ser Thr Pro Pro Ser Gly Thr Glu Asn Lys Pro Ala Thr Gly
1 5 10 15
<210> 95
<211> 6
<212> PRT
<213> 人工序列
<400> 95
Ser Tyr Trp Lys Gly Ser
1 5
<210> 96
<211> 8
<212> PRT
<213> 人工序列
<400> 96
Glu Ala Ala Lys Glu Ala Ala Lys
1 5
<210> 97
<211> 7
<212> PRT
<213> 人工序列
<400> 97
Thr Ser Tyr Trp Lys Gly Ser
1 5
<210> 98
<211> 4
<212> PRT
<213> 人工序列
<400> 98
Gly Gly Ser Gly
1
<210> 99
<211> 5
<212> PRT
<213> 人工序列
<400> 99
Gly Gly Ala Ser Gly
1 5
<210> 100
<211> 15
<212> PRT
<213> 人工序列
<400> 100
Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val
1 5 10 15
<210> 101
<211> 15
<212> PRT
<213> 人工序列
<400> 101
Arg Ser Tyr Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly
1 5 10 15
<210> 102
<211> 15
<212> PRT
<213> 人工序列
<400> 102
Gly Lys Thr Phe Pro Pro Thr Glu Pro Lys Lys Asp Lys Lys Gly
1 5 10 15
<210> 103
<211> 15
<212> PRT
<213> 人工序列
<400> 103
Met Tyr Ser Phe Val Ser Glu Glu Thr Gly Thr Leu Ile Val Asn
1 5 10 15
<210> 104
<211> 15
<212> PRT
<213> 人工序列
<400> 104
Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr
1 5 10 15
<210> 105
<211> 15
<212> PRT
<213> 人工序列
<400> 105
Gly Gly Met Lys Asp Leu Ser Pro Arg Trp Tyr Phe Gly Gly Gly
1 5 10 15
<210> 106
<211> 15
<212> PRT
<213> 人工序列
<400> 106
Gly Ser Lys Ser Pro Ile Gln Tyr Ile Asp Gly Gly Gly Gly Gly
1 5 10 15
<210> 107
<211> 15
<212> PRT
<213> 人工序列
<400> 107
Tyr Ile Arg Gly Ala Arg Lys Ser Ala Pro Leu Ile Glu Leu Gly
1 5 10 15
<210> 108
<211> 1041
<212> DNA
<213> 人工序列
<400> 108
atggttaatt atctcggagc acacgctttc gagcgcgaca tctcaacgga aatttatcaa 60
gccggttcaa ccatgaagat caagctccgt atggaagggg cggtcaacgg tcacaaattc 120
gtcatcgaag gggaaggcat tggcaagcca tacgaaggga cacagacttt ggacctcact 180
gtggaagaag gttcatctgg tgaagcggcg aaggaagcgg ccaagggaag cacaccatgc 240
aacggcgtgg aaggtttcaa ttgctacttt tacgacatcc ttaccccggc gttccaatat 300
ggtaaccgtg ccttcacgaa gtacccagaa gatatccctg attactttaa gcaggcattt 360
cctgaaggtt attcgtggga gcgcagtatg acctatgagg accaaggtat ttgtatcgcg 420
acgagcgaca ttaccatgga aggggactgt ttcttctacg agattcgctt cgatggaact 480
aattcgaata acctggacag taaagttggt ggcaactaca actatacctt aaaatgggag 540
ccaagtacag aaaagatgta cgttgaagac ggggtgttga agggtgacgt ggaaatggca 600
ttactcttgt ttgagcgcga catttcaacc gagatttacc aagccgggtc gacaggcggg 660
tccggaacaa gctactggaa ggggagtcac tatcgctgtg attttaagac gacctacaaa 720
gctggtagca ctccatgtaa cggagtagag gggttcaact gctactttca tgaagtagat 780
caccgtattg agattttatc acactacttt cctctgcaat cgtatggctt ccaacccacg 840
aatggcgttg gtagtagcgg cgaagccgcc aaggaagcag ccaagaaggt gcgcctgtac 900
gagcacgccg aggcgtactt tcctctccag tcctatggat tccaacctac caatggagtt 960
ggcggctcgg gcggcggtgc ttccgggaat tcgaacaact tagatagcaa ggtgggtggg 1020
aactataatt atctcgagta g 1041
<210> 109
<211> 1059
<212> DNA
<213> 人工序列
<400> 109
atggttaatt atctcggagc acacgctttc gagcgcgaca tctcaacgga aatttatcaa 60
gccggttcaa ccatgaagat caagctccgt atggaagggg cggtcaacgg tcacaaattc 120
gtcatcgaag gggaaggcat tggcaagcca tacgaaggga cacagacttt ggacctcact 180
gtggaagaag gttcatctgg tgaagcggcg aaggaagcgg ccaagggaag cacaccatgc 240
aacggcgtgg aaggtttcaa ttgctacttt tacgacatcc ttaccccggc gttccaatat 300
ggtaaccgtg ccttcacgaa gtacccagaa gatatccctg attactttaa gcaggcattt 360
cctgaaggtt attcgtggga gcgcagtatg acctatgagg accaaggtat ttgtatcgcg 420
acgagcgaca ttaccatgga aggggactgt ttcttctacg agattcgctt cgatggaact 480
aattcgaata acctggacag taaagttggt ggcaactaca actatacctt aaaatgggag 540
ccaagtacag aaaagatgta cgttgaagac ggggtgttga agggtgacgt ggaaatggca 600
ttactcttgt ttgagcgcga catttcaacc gagatttacc aagccgggtc gacaggcggg 660
tccggaacaa gctactggaa ggggagtcac tatcgctgtg attttaagac gacctacaaa 720
gctggtagca ctccatgtaa cggagtagag gggttcaact gctactttca tgaagtagat 780
caccgtattg agattttatc acactacttt cctctgcaat cgtatggctt ccaacccacg 840
aatggcgttg gtagtagcgg cgaagccgcc aaggaagcag ccaagaaggt gcgcctgtac 900
gagcacgccg aggcgtactt tcctctccag tcctatggat tccaacctac caatggagtt 960
ggcggctcgg gcggcggtgc ttccgggaat tcgaacaact tagatagcaa ggtgggtggg 1020
aactataatt atctcgagca ccaccaccac caccactga 1059
<210> 110
<211> 1128
<212> DNA
<213> 人工序列
<400> 110
atggtaaatt atatagggtc aagtggagtt gtcaacccgg tgatgggtgg ctcgggtggt 60
ccagcgccag cgccgatgaa aattaagttg cgtatggaag gggcggttaa tgctccgcgt 120
atcaccttcg gcggtcctag cgatagcacc ggcggtggtt ctggcgaagc cgcgaagacg 180
agctactgga agggttcgca taaattcgtg attgagggtg agggcattgg taaaccgtat 240
gagggtacgc agaccttaga tctgaccgtt gaggaaggtt ctagcggcgt cgttaacccg 300
gttatgtatg atattttgac cccggcgttc caatatggaa accgcgcatt caccaaatac 360
ccggaatata ttcgtgttgg tgcccgtaaa agcgctccgc tgatcgagct gggttattcc 420
tgggagcgct ccatgaccta cggctccctg atcgacctgc aagagttggg taagtacgag 480
caatacatcg aggcagccgc taaagaagcc gcagcgaagg gcggcgcttc tggcatctgc 540
attgcgacca gcgacatcac catggagggc gactgttttt tctatgaaat ccgcttcgat 600
ggcaccggtc cgtttcagca gtttggacgt gatatcgcgg ataccacgga tgcgaccctg 660
aagtgggagc cgtccactga aaaaatgtac gtcgaggacg gtgtgctgaa gggtgacgtt 720
gaaatggcgc tgctccttgg tggctccggc acgtcatact ggaaaggttc tatgtggctg 780
tcttacttca tcgccagctt tcgtctgcat tatagatgcg attttaaaac tacgtacaaa 840
gcacgcagct acaccccggg cgactccagc agcggctgga ccgcacatga agtggatcat 900
cgtattgaga tcttaagtca cattgtggac gaaccgggcg gtgcgagcgg caaggtgcgt 960
ctgtatgagc acgcggaagc gccggcgccg gctccgggtt ttagcgcatt ggaaccgctg 1020
gtagacctgc cgggcggcag cggtggtggt gcgagcggga agaccttccc gcctacagaa 1080
ccgaaaaagg acaaaaaggg tcatcaccac caccaccaca agaagtaa 1128
<210> 111
<211> 1074
<212> DNA
<213> 人工序列
<400> 111
atggtaaatt acatactagg agtttatcac aagaacaaca aaagctggat ggagagcgaa 60
ttccgcgttt atccggcacc ggcgcctatg aaaatcaagc tgcgtatgga aggtgcagtt 120
aatggtcata aattcgtgat tgagggtgaa ggcattggca aaccaggtgg ttcaggtgag 180
gctgcgaagt tcaactgcta ttttccgctg cagagctacg gctttcagcc gacgggtacg 240
cagaccctgg atctgacggt cgaggaaccg ttgcaatcgt acggtttcca accgacctat 300
gacatcctga ccccggcgtt ccagtatggc aaccgcgcgt tcaccaaata cccggaagcc 360
ggtaacggtg gcgatgccgc cctcgctctg ttactgttag atggctacag ctgggaacgt 420
agcatgacgt acggccgttc ctacctgacc ccgggtgaca gcagctccgg tggcgcgtcg 480
ggtggtatct gcattgcgac cagtgatatt acgatggagg gtgactgttt tttttatgag 540
atccgctttg atggtaccgc ggaccagttg accccaactt ggcgtgtgac ccttaagtgg 600
gagccgagca ccgaaaaaat gtatgtagag gatggggtgc tgaagggcga cgttgaaatg 660
gcattgttgt tgtttatcta taataaaatc gtggacgaac cgggtggcag cggtacttct 720
tactggaaag gttcccatta tcgttgcgac ttcaaaacca cctacaaagc aaagaacccg 780
ttgctatacg atgcgaatta ccatgaagtt gaccatcgta ttgaaattct gagccacggc 840
ggctctggag gcgaggctgc taagggtaga cctcaaggtc tgccgaataa caccgcatcc 900
aaagttcgtc tgtacgagca cgcggaggcg ctggcggaga tcctgcaaaa aaacctgatc 960
cgccagggta cagattataa gcattggccg caaattgcgg gcggctccgg tggcggcaag 1020
atcgccgact acaattacaa gctgggccat caccaccacc accacaagaa gtaa 1074
<210> 112
<211> 1119
<212> DNA
<213> 人工序列
<400> 112
atggtaaatt atatatttaa ctgttacttc ccgctgcaga gctacggctt ccagccgacc 60
aatggtgtga tgaaaatcaa actgcgtatg gaaggcgcag ttcgtccgca gggtctgccg 120
aataacaccg caagcggcgg ttccggtggc gaggcggcga agcataagtt cgtgattgaa 180
ggtgagggta ttggtaagcc ggaagctgcg aaagaagctg ctaagggctc tggcttcatc 240
tataacaaaa tcgttgatga gccgggtgcg ggtacgcaga ccctggatct gactgtagag 300
gaagcggacc aactgacccc gacctggcgt gtgggctatg acatcttgac tccggcgttt 360
caatatggta atagagcatt caccaaatac ccggagggca agatcgccga ctacaactac 420
aagttgggtg gctacagctg ggaacgctct atgacctacg aagatcaagg tatttgtatt 480
gcgaccagcg atatcaccat ggagggtgac tgcttttttt atgaaatccg ctttgatggt 540
acatacattc gcgtgggtgc gcgtaaaagc gctccgctga ttgagctgac gctgaaatgg 600
gagccgagca ccgaaaaaat gtatgtcgag atcgtggacg aaccgggagg gtccggtggt 660
gttctgaagg gcgacgttga gatggcactg ttgttgaaga acccgttatt gtacgatgca 720
aattacgggg gttcgggcac ctcctattgg aaaggtcatt atcgctgcga tttcaaaacc 780
acctataaag cgaagacctt tccgccgacg gagcctaaaa aagataaaaa gcacgaagtt 840
gaccatcgta ttgagatcct gagccatgaa gcggctaagg gcggtgccag cggccgtagc 900
tacctcactc cgggtgacag ctctagcaaa gttcgtctgt atgagcacgc agaagccccg 960
gcgccagcgc caggctcgtc cggtgtcgtg aacccggtca tggagccgat ttacgacggc 1020
ggctccggcg gtgcgccagg ccagacggga aagatcgccg actataacta caagcttggt 1080
gcgtcaggca aacaccatca ccaccaccac aagaagtaa 1119
<210> 113
<211> 975
<212> DNA
<213> 人工序列
<400> 113
atggtcaatt atatcgcgct cccacaacgc caaaagaagc agcagaccgt gacgctgttg 60
ccggcaccgg cacccatgaa gattaagtta cgtatggaag gagcggtcaa tgggcacaag 120
tttgtcatcg agggcgaagg aatcgggaaa ccttacgaag ggacccaaac attagatctg 180
accgttgaag agggaagcaa gagcccaatc caatacattg attacgatat tcttacgcct 240
gcatttcagt acggcaatcg tgctttcaca aagtaccctg aagacttctt ggagtatcac 300
gacgtgcgcg tagttttaga cttcgggtat tcttgggaac gtagtatgac gtatggtgga 360
gctagcggtg gtatcaatgc aagtgttgtc aacatccagg gaatctgcat cgccacctcg 420
gatatcacta tggaaggcgg gtccggggaa gctgcgaagc aattcgcccc ctcggctagt 480
gccttcttct gcttcttcta cgaaatccgt tttgacggta ccatgtatag cttcgtaagc 540
gaagaaacgg gcacgctgat tgtcaatact ctgaagtggg agccgtctac ggaaaagatg 600
tatgtagagg acggcgtact gaagggcgac gtcgagatgg cgcttctgtt agaaggcggc 660
ggtcattacc gttgcgattt taagacaacg tataaggcac catccggtac ttggttaact 720
tacacaggcc acgaggtcga ccatcgtatc gagatcttat cacatggcgg ttccggcggc 780
gaagcggcca aggggcagtt cgcgcctagt gcatcggctt tcttcaaggt tcgcctctat 840
gaacacgccg aggcaggcgg tgcatctgga gagctggaca aatatggcgg ttcgggcggc 900
ggtatgtaca gtttcgtatc ggaagagaca ggaactttaa ttgtgaatca ccatcaccac 960
caccataaga agtaa 975
<210> 114
<211> 996
<212> DNA
<213> 人工序列
<400> 114
atggtgaatt acatcccgct ccaatcatac ggatttcagc caacgaatgg ggtcgggtac 60
cctgcgccag cacccgcaat gaaaatcaag cttcgtatgg aaggtgcagt taatggacac 120
aagttcgtga tcgagggcga gggcattggc aagccctatg aagggaccca aactttggac 180
ttgacggtag aagagggtat ctatcagacc agtaattttc gtgtctacga catcttgact 240
ccggctttcc aatacgggaa ccgcgcgttc actaagtacc ctgagaaggc gtacaatgtg 300
acccaagcat tcgggcgtcg tggccctgaa ggctatagct gggaacgttc tatgacgtac 360
gaggatcaag gtatctgtat tgcgactagc gatattacaa tggaaggcac caatacatct 420
aatcaagtgg cggtgggtgg aagcggtgag gcagcaaagt gcttctttta tgagatccgc 480
ttcgatggta ctaacccggt cctgcccttt aacgatggag tttatttcgc ctcaaccaca 540
ttgaaatggg agccctcaac tgaaaagatg tatgttgaag acggcgtttt gaagggtgac 600
gtagagatgg cacttctgct gtacaactac aagcttcccg atgacttcac tggcggcagc 660
ggtacaagtt attggaaggg ttcacattat cgctgtgatt tcaagacaac ctataaagca 720
atgttccatc tggtagactt tcaagttacg attgctgaga tccttcatga ggttgatcac 780
cgtatcgaaa tcctttctca cggcggaagc ggcggagagg cggccaaggg tatgaaggac 840
ttgagccctc gctggtattt caaggtccgc ttatacgagc acgccgaggc cgacgctgcc 900
cttgcgctcc tgttattaga cggcggaagc ggtggtggca tgaaggattt atcccctcgc 960
tggtacttcc atcaccatca ccaccacaag aagtga 996
<210> 115
<211> 1059
<212> DNA
<213> 人工序列
<400> 115
atggtgaatt atatcttagg ggtgtaccac aagaataaca agtcatggat ggagtcggaa 60
tttcgtgtgt acccggcccc ggctcccatg aagatcaagt tacgcatgga aggcgccgtt 120
aacggccaca aattcgtgat cgagggcgaa ggaatcggta agccaggtgg ctcgggtgaa 180
gccgccaagt tcatttacaa taagatcgtt gatgaaccag gaacacaaac tttagatctt 240
accgtagagg agaagaaccc gcttctttac gacgccaatt actatgacat tttaacgccg 300
gccttccaat acggcaatcg cgcttttacg aagtatccgg aagcgggtaa cggcggcgat 360
gcagccttag cattattatt actggacggt tattcgtggg agcgttcaat gacgtatggc 420
cgtagttact tgacccccgg agacagtagc tctggtggtg ccagcggcgg gatctgtatt 480
gcaactagtg atatcaccat ggaaggcgac tgcttcttct atgagattcg tttcgatggg 540
accgccgatc aactgacccc tacctggcgt gtaacattga agtgggagcc aagcactgag 600
aagatgtacg tggaagacgg cgttctgaag ggcgacgtgg agatggcctt gttattattc 660
atctacaata agatcgtgga cgagccgggt ggtagcggta catcctactg gaagggttcg 720
cattaccgtt gtgatttcaa gacaacctat aaggctaaga atccgttatt gtatgacgca 780
aattaccatg aggtggacca ccgtatcgaa atcctttccc atggcggaag cggtggtgag 840
gcggcgaagg gtcgcccgca gggactgccg aataatacgg cgtctaaggt tcgcttatac 900
gaacacgctg aggccctcgc cgagatcctg caaaagaact taatccgcca aggaaccgac 960
tataagcact ggccgcaaat cgccggtggc tccggtggtg gtaagatcgc agactacaac 1020
tataagctcg gtcatcatca tcatcaccat aagaaataa 1059
<210> 116
<211> 346
<212> PRT
<213> 人工序列
<400> 116
Met Val Asn Tyr Leu Gly Ala His Ala Phe Glu Arg Asp Ile Ser Thr
1 5 10 15
Glu Ile Tyr Gln Ala Gly Ser Thr Met Lys Ile Lys Leu Arg Met Glu
20 25 30
Gly Ala Val Asn Gly His Lys Phe Val Ile Glu Gly Glu Gly Ile Gly
35 40 45
Lys Pro Tyr Glu Gly Thr Gln Thr Leu Asp Leu Thr Val Glu Glu Gly
50 55 60
Ser Ser Gly Glu Ala Ala Lys Glu Ala Ala Lys Gly Ser Thr Pro Cys
65 70 75 80
Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Tyr Asp Ile Leu Thr Pro
85 90 95
Ala Phe Gln Tyr Gly Asn Arg Ala Phe Thr Lys Tyr Pro Glu Asp Ile
100 105 110
Pro Asp Tyr Phe Lys Gln Ala Phe Pro Glu Gly Tyr Ser Trp Glu Arg
115 120 125
Ser Met Thr Tyr Glu Asp Gln Gly Ile Cys Ile Ala Thr Ser Asp Ile
130 135 140
Thr Met Glu Gly Asp Cys Phe Phe Tyr Glu Ile Arg Phe Asp Gly Thr
145 150 155 160
Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Thr
165 170 175
Leu Lys Trp Glu Pro Ser Thr Glu Lys Met Tyr Val Glu Asp Gly Val
180 185 190
Leu Lys Gly Asp Val Glu Met Ala Leu Leu Leu Phe Glu Arg Asp Ile
195 200 205
Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Gly Gly Ser Gly Thr Ser
210 215 220
Tyr Trp Lys Gly Ser His Tyr Arg Cys Asp Phe Lys Thr Thr Tyr Lys
225 230 235 240
Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe
245 250 255
His Glu Val Asp His Arg Ile Glu Ile Leu Ser His Tyr Phe Pro Leu
260 265 270
Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Ser Ser Gly Glu
275 280 285
Ala Ala Lys Glu Ala Ala Lys Lys Val Arg Leu Tyr Glu His Ala Glu
290 295 300
Ala Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val
305 310 315 320
Gly Gly Ser Gly Gly Gly Ala Ser Gly Asn Ser Asn Asn Leu Asp Ser
325 330 335
Lys Val Gly Gly Asn Tyr Asn Tyr Leu Glu
340 345
<210> 117
<211> 352
<212> PRT
<213> 人工序列
<400> 117
Met Val Asn Tyr Leu Gly Ala His Ala Phe Glu Arg Asp Ile Ser Thr
1 5 10 15
Glu Ile Tyr Gln Ala Gly Ser Thr Met Lys Ile Lys Leu Arg Met Glu
20 25 30
Gly Ala Val Asn Gly His Lys Phe Val Ile Glu Gly Glu Gly Ile Gly
35 40 45
Lys Pro Tyr Glu Gly Thr Gln Thr Leu Asp Leu Thr Val Glu Glu Gly
50 55 60
Ser Ser Gly Glu Ala Ala Lys Glu Ala Ala Lys Gly Ser Thr Pro Cys
65 70 75 80
Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Tyr Asp Ile Leu Thr Pro
85 90 95
Ala Phe Gln Tyr Gly Asn Arg Ala Phe Thr Lys Tyr Pro Glu Asp Ile
100 105 110
Pro Asp Tyr Phe Lys Gln Ala Phe Pro Glu Gly Tyr Ser Trp Glu Arg
115 120 125
Ser Met Thr Tyr Glu Asp Gln Gly Ile Cys Ile Ala Thr Ser Asp Ile
130 135 140
Thr Met Glu Gly Asp Cys Phe Phe Tyr Glu Ile Arg Phe Asp Gly Thr
145 150 155 160
Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Thr
165 170 175
Leu Lys Trp Glu Pro Ser Thr Glu Lys Met Tyr Val Glu Asp Gly Val
180 185 190
Leu Lys Gly Asp Val Glu Met Ala Leu Leu Leu Phe Glu Arg Asp Ile
195 200 205
Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Gly Gly Ser Gly Thr Ser
210 215 220
Tyr Trp Lys Gly Ser His Tyr Arg Cys Asp Phe Lys Thr Thr Tyr Lys
225 230 235 240
Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe
245 250 255
His Glu Val Asp His Arg Ile Glu Ile Leu Ser His Tyr Phe Pro Leu
260 265 270
Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Ser Ser Gly Glu
275 280 285
Ala Ala Lys Glu Ala Ala Lys Lys Val Arg Leu Tyr Glu His Ala Glu
290 295 300
Ala Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val
305 310 315 320
Gly Gly Ser Gly Gly Gly Ala Ser Gly Asn Ser Asn Asn Leu Asp Ser
325 330 335
Lys Val Gly Gly Asn Tyr Asn Tyr Leu Glu His His His His His His
340 345 350
<210> 118
<211> 375
<212> PRT
<213> 人工序列
<400> 118
Met Val Asn Tyr Ile Gly Ser Ser Gly Val Val Asn Pro Val Met Gly
1 5 10 15
Gly Ser Gly Gly Pro Ala Pro Ala Pro Met Lys Ile Lys Leu Arg Met
20 25 30
Glu Gly Ala Val Asn Ala Pro Arg Ile Thr Phe Gly Gly Pro Ser Asp
35 40 45
Ser Thr Gly Gly Gly Ser Gly Glu Ala Ala Lys Thr Ser Tyr Trp Lys
50 55 60
Gly Ser His Lys Phe Val Ile Glu Gly Glu Gly Ile Gly Lys Pro Tyr
65 70 75 80
Glu Gly Thr Gln Thr Leu Asp Leu Thr Val Glu Glu Gly Ser Ser Gly
85 90 95
Val Val Asn Pro Val Met Tyr Asp Ile Leu Thr Pro Ala Phe Gln Tyr
100 105 110
Gly Asn Arg Ala Phe Thr Lys Tyr Pro Glu Tyr Ile Arg Val Gly Ala
115 120 125
Arg Lys Ser Ala Pro Leu Ile Glu Leu Gly Tyr Ser Trp Glu Arg Ser
130 135 140
Met Thr Tyr Gly Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu
145 150 155 160
Gln Tyr Ile Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Gly Gly Ala
165 170 175
Ser Gly Ile Cys Ile Ala Thr Ser Asp Ile Thr Met Glu Gly Asp Cys
180 185 190
Phe Phe Tyr Glu Ile Arg Phe Asp Gly Thr Gly Pro Phe Gln Gln Phe
195 200 205
Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Thr Leu Lys Trp Glu Pro
210 215 220
Ser Thr Glu Lys Met Tyr Val Glu Asp Gly Val Leu Lys Gly Asp Val
225 230 235 240
Glu Met Ala Leu Leu Leu Gly Gly Ser Gly Thr Ser Tyr Trp Lys Gly
245 250 255
Ser Met Trp Leu Ser Tyr Phe Ile Ala Ser Phe Arg Leu His Tyr Arg
260 265 270
Cys Asp Phe Lys Thr Thr Tyr Lys Ala Arg Ser Tyr Thr Pro Gly Asp
275 280 285
Ser Ser Ser Gly Trp Thr Ala His Glu Val Asp His Arg Ile Glu Ile
290 295 300
Leu Ser His Ile Val Asp Glu Pro Gly Gly Ala Ser Gly Lys Val Arg
305 310 315 320
Leu Tyr Glu His Ala Glu Ala Pro Ala Pro Ala Pro Gly Phe Ser Ala
325 330 335
Leu Glu Pro Leu Val Asp Leu Pro Gly Gly Ser Gly Gly Gly Ala Ser
340 345 350
Gly Lys Thr Phe Pro Pro Thr Glu Pro Lys Lys Asp Lys Lys Gly His
355 360 365
His His His His His Lys Lys
370 375
<210> 119
<211> 357
<212> PRT
<213> 人工序列
<400> 119
Met Val Asn Tyr Ile Leu Gly Val Tyr His Lys Asn Asn Lys Ser Trp
1 5 10 15
Met Glu Ser Glu Phe Arg Val Tyr Pro Ala Pro Ala Pro Met Lys Ile
20 25 30
Lys Leu Arg Met Glu Gly Ala Val Asn Gly His Lys Phe Val Ile Glu
35 40 45
Gly Glu Gly Ile Gly Lys Pro Gly Gly Ser Gly Glu Ala Ala Lys Phe
50 55 60
Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Gly Thr
65 70 75 80
Gln Thr Leu Asp Leu Thr Val Glu Glu Pro Leu Gln Ser Tyr Gly Phe
85 90 95
Gln Pro Thr Tyr Asp Ile Leu Thr Pro Ala Phe Gln Tyr Gly Asn Arg
100 105 110
Ala Phe Thr Lys Tyr Pro Glu Ala Gly Asn Gly Gly Asp Ala Ala Leu
115 120 125
Ala Leu Leu Leu Leu Asp Gly Tyr Ser Trp Glu Arg Ser Met Thr Tyr
130 135 140
Gly Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Gly Ala Ser
145 150 155 160
Gly Gly Ile Cys Ile Ala Thr Ser Asp Ile Thr Met Glu Gly Asp Cys
165 170 175
Phe Phe Tyr Glu Ile Arg Phe Asp Gly Thr Ala Asp Gln Leu Thr Pro
180 185 190
Thr Trp Arg Val Thr Leu Lys Trp Glu Pro Ser Thr Glu Lys Met Tyr
195 200 205
Val Glu Asp Gly Val Leu Lys Gly Asp Val Glu Met Ala Leu Leu Leu
210 215 220
Phe Ile Tyr Asn Lys Ile Val Asp Glu Pro Gly Gly Ser Gly Thr Ser
225 230 235 240
Tyr Trp Lys Gly Ser His Tyr Arg Cys Asp Phe Lys Thr Thr Tyr Lys
245 250 255
Ala Lys Asn Pro Leu Leu Tyr Asp Ala Asn Tyr His Glu Val Asp His
260 265 270
Arg Ile Glu Ile Leu Ser His Gly Gly Ser Gly Gly Glu Ala Ala Lys
275 280 285
Gly Arg Pro Gln Gly Leu Pro Asn Asn Thr Ala Ser Lys Val Arg Leu
290 295 300
Tyr Glu His Ala Glu Ala Leu Ala Glu Ile Leu Gln Lys Asn Leu Ile
305 310 315 320
Arg Gln Gly Thr Asp Tyr Lys His Trp Pro Gln Ile Ala Gly Gly Ser
325 330 335
Gly Gly Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Gly His His His
340 345 350
His His His Lys Lys
355
<210> 120
<211> 372
<212> PRT
<213> 人工序列
<400> 120
Met Val Asn Tyr Ile Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly
1 5 10 15
Phe Gln Pro Thr Asn Gly Val Met Lys Ile Lys Leu Arg Met Glu Gly
20 25 30
Ala Val Arg Pro Gln Gly Leu Pro Asn Asn Thr Ala Ser Gly Gly Ser
35 40 45
Gly Gly Glu Ala Ala Lys His Lys Phe Val Ile Glu Gly Glu Gly Ile
50 55 60
Gly Lys Pro Glu Ala Ala Lys Glu Ala Ala Lys Gly Ser Gly Phe Ile
65 70 75 80
Tyr Asn Lys Ile Val Asp Glu Pro Gly Ala Gly Thr Gln Thr Leu Asp
85 90 95
Leu Thr Val Glu Glu Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Gly
100 105 110
Tyr Asp Ile Leu Thr Pro Ala Phe Gln Tyr Gly Asn Arg Ala Phe Thr
115 120 125
Lys Tyr Pro Glu Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Gly Gly
130 135 140
Tyr Ser Trp Glu Arg Ser Met Thr Tyr Glu Asp Gln Gly Ile Cys Ile
145 150 155 160
Ala Thr Ser Asp Ile Thr Met Glu Gly Asp Cys Phe Phe Tyr Glu Ile
165 170 175
Arg Phe Asp Gly Thr Tyr Ile Arg Val Gly Ala Arg Lys Ser Ala Pro
180 185 190
Leu Ile Glu Leu Thr Leu Lys Trp Glu Pro Ser Thr Glu Lys Met Tyr
195 200 205
Val Glu Ile Val Asp Glu Pro Gly Gly Ser Gly Gly Val Leu Lys Gly
210 215 220
Asp Val Glu Met Ala Leu Leu Leu Lys Asn Pro Leu Leu Tyr Asp Ala
225 230 235 240
Asn Tyr Gly Gly Ser Gly Thr Ser Tyr Trp Lys Gly His Tyr Arg Cys
245 250 255
Asp Phe Lys Thr Thr Tyr Lys Ala Lys Thr Phe Pro Pro Thr Glu Pro
260 265 270
Lys Lys Asp Lys Lys His Glu Val Asp His Arg Ile Glu Ile Leu Ser
275 280 285
His Glu Ala Ala Lys Gly Gly Ala Ser Gly Arg Ser Tyr Leu Thr Pro
290 295 300
Gly Asp Ser Ser Ser Lys Val Arg Leu Tyr Glu His Ala Glu Ala Pro
305 310 315 320
Ala Pro Ala Pro Gly Ser Ser Gly Val Val Asn Pro Val Met Glu Pro
325 330 335
Ile Tyr Asp Gly Gly Ser Gly Gly Ala Pro Gly Gln Thr Gly Lys Ile
340 345 350
Ala Asp Tyr Asn Tyr Lys Leu Gly Ala Ser Gly Lys His His His His
355 360 365
His His Lys Lys
370
<210> 121
<211> 324
<212> PRT
<213> 人工序列
<400> 121
Met Val Asn Tyr Ile Ala Leu Pro Gln Arg Gln Lys Lys Gln Gln Thr
1 5 10 15
Val Thr Leu Leu Pro Ala Pro Ala Pro Met Lys Ile Lys Leu Arg Met
20 25 30
Glu Gly Ala Val Asn Gly His Lys Phe Val Ile Glu Gly Glu Gly Ile
35 40 45
Gly Lys Pro Tyr Glu Gly Thr Gln Thr Leu Asp Leu Thr Val Glu Glu
50 55 60
Gly Ser Lys Ser Pro Ile Gln Tyr Ile Asp Tyr Asp Ile Leu Thr Pro
65 70 75 80
Ala Phe Gln Tyr Gly Asn Arg Ala Phe Thr Lys Tyr Pro Glu Asp Phe
85 90 95
Leu Glu Tyr His Asp Val Arg Val Val Leu Asp Phe Gly Tyr Ser Trp
100 105 110
Glu Arg Ser Met Thr Tyr Gly Gly Ala Ser Gly Gly Ile Asn Ala Ser
115 120 125
Val Val Asn Ile Gln Gly Ile Cys Ile Ala Thr Ser Asp Ile Thr Met
130 135 140
Glu Gly Gly Ser Gly Glu Ala Ala Lys Gln Phe Ala Pro Ser Ala Ser
145 150 155 160
Ala Phe Phe Cys Phe Phe Tyr Glu Ile Arg Phe Asp Gly Thr Met Tyr
165 170 175
Ser Phe Val Ser Glu Glu Thr Gly Thr Leu Ile Val Asn Thr Leu Lys
180 185 190
Trp Glu Pro Ser Thr Glu Lys Met Tyr Val Glu Asp Gly Val Leu Lys
195 200 205
Gly Asp Val Glu Met Ala Leu Leu Leu Glu Gly Gly Gly His Tyr Arg
210 215 220
Cys Asp Phe Lys Thr Thr Tyr Lys Ala Pro Ser Gly Thr Trp Leu Thr
225 230 235 240
Tyr Thr Gly His Glu Val Asp His Arg Ile Glu Ile Leu Ser His Gly
245 250 255
Gly Ser Gly Gly Glu Ala Ala Lys Gly Gln Phe Ala Pro Ser Ala Ser
260 265 270
Ala Phe Phe Lys Val Arg Leu Tyr Glu His Ala Glu Ala Gly Gly Ala
275 280 285
Ser Gly Glu Leu Asp Lys Tyr Gly Gly Ser Gly Gly Gly Met Tyr Ser
290 295 300
Phe Val Ser Glu Glu Thr Gly Thr Leu Ile Val Asn His His His His
305 310 315 320
His His Lys Lys
<210> 122
<211> 331
<212> PRT
<213> 人工序列
<400> 122
Met Val Asn Tyr Ile Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn
1 5 10 15
Gly Val Gly Tyr Pro Ala Pro Ala Pro Ala Met Lys Ile Lys Leu Arg
20 25 30
Met Glu Gly Ala Val Asn Gly His Lys Phe Val Ile Glu Gly Glu Gly
35 40 45
Ile Gly Lys Pro Tyr Glu Gly Thr Gln Thr Leu Asp Leu Thr Val Glu
50 55 60
Glu Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Tyr Asp Ile Leu Thr
65 70 75 80
Pro Ala Phe Gln Tyr Gly Asn Arg Ala Phe Thr Lys Tyr Pro Glu Lys
85 90 95
Ala Tyr Asn Val Thr Gln Ala Phe Gly Arg Arg Gly Pro Glu Gly Tyr
100 105 110
Ser Trp Glu Arg Ser Met Thr Tyr Glu Asp Gln Gly Ile Cys Ile Ala
115 120 125
Thr Ser Asp Ile Thr Met Glu Gly Thr Asn Thr Ser Asn Gln Val Ala
130 135 140
Val Gly Gly Ser Gly Glu Ala Ala Lys Cys Phe Phe Tyr Glu Ile Arg
145 150 155 160
Phe Asp Gly Thr Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe
165 170 175
Ala Ser Thr Thr Leu Lys Trp Glu Pro Ser Thr Glu Lys Met Tyr Val
180 185 190
Glu Asp Gly Val Leu Lys Gly Asp Val Glu Met Ala Leu Leu Leu Tyr
195 200 205
Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Gly Ser Gly Thr Ser Tyr
210 215 220
Trp Lys Gly Ser His Tyr Arg Cys Asp Phe Lys Thr Thr Tyr Lys Ala
225 230 235 240
Met Phe His Leu Val Asp Phe Gln Val Thr Ile Ala Glu Ile Leu His
245 250 255
Glu Val Asp His Arg Ile Glu Ile Leu Ser His Gly Gly Ser Gly Gly
260 265 270
Glu Ala Ala Lys Gly Met Lys Asp Leu Ser Pro Arg Trp Tyr Phe Lys
275 280 285
Val Arg Leu Tyr Glu His Ala Glu Ala Asp Ala Ala Leu Ala Leu Leu
290 295 300
Leu Leu Asp Gly Gly Ser Gly Gly Gly Met Lys Asp Leu Ser Pro Arg
305 310 315 320
Trp Tyr Phe His His His His His His Lys Lys
325 330
<210> 123
<211> 352
<212> PRT
<213> 人工序列
<400> 123
Met Val Asn Tyr Ile Leu Gly Val Tyr His Lys Asn Asn Lys Ser Trp
1 5 10 15
Met Glu Ser Glu Phe Arg Val Tyr Pro Ala Pro Ala Pro Met Lys Ile
20 25 30
Lys Leu Arg Met Glu Gly Ala Val Asn Gly His Lys Phe Val Ile Glu
35 40 45
Gly Glu Gly Ile Gly Lys Pro Gly Gly Ser Gly Glu Ala Ala Lys Phe
50 55 60
Ile Tyr Asn Lys Ile Val Asp Glu Pro Gly Thr Gln Thr Leu Asp Leu
65 70 75 80
Thr Val Glu Glu Lys Asn Pro Leu Leu Tyr Asp Ala Asn Tyr Tyr Asp
85 90 95
Ile Leu Thr Pro Ala Phe Gln Tyr Gly Asn Arg Ala Phe Thr Lys Tyr
100 105 110
Pro Glu Ala Gly Asn Gly Gly Asp Ala Ala Leu Ala Leu Leu Leu Leu
115 120 125
Asp Gly Tyr Ser Trp Glu Arg Ser Met Thr Tyr Gly Arg Ser Tyr Leu
130 135 140
Thr Pro Gly Asp Ser Ser Ser Gly Gly Ala Ser Gly Gly Ile Cys Ile
145 150 155 160
Ala Thr Ser Asp Ile Thr Met Glu Gly Asp Cys Phe Phe Tyr Glu Ile
165 170 175
Arg Phe Asp Gly Thr Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Thr
180 185 190
Leu Lys Trp Glu Pro Ser Thr Glu Lys Met Tyr Val Glu Asp Gly Val
195 200 205
Leu Lys Gly Asp Val Glu Met Ala Leu Leu Leu Phe Ile Tyr Asn Lys
210 215 220
Ile Val Asp Glu Pro Gly Gly Ser Gly Thr Ser Tyr Trp Lys Gly Ser
225 230 235 240
His Tyr Arg Cys Asp Phe Lys Thr Thr Tyr Lys Ala Lys Asn Pro Leu
245 250 255
Leu Tyr Asp Ala Asn Tyr His Glu Val Asp His Arg Ile Glu Ile Leu
260 265 270
Ser His Gly Gly Ser Gly Gly Glu Ala Ala Lys Gly Arg Pro Gln Gly
275 280 285
Leu Pro Asn Asn Thr Ala Ser Lys Val Arg Leu Tyr Glu His Ala Glu
290 295 300
Ala Leu Ala Glu Ile Leu Gln Lys Asn Leu Ile Arg Gln Gly Thr Asp
305 310 315 320
Tyr Lys His Trp Pro Gln Ile Ala Gly Gly Ser Gly Gly Gly Lys Ile
325 330 335
Ala Asp Tyr Asn Tyr Lys Leu Gly His His His His His His Lys Lys
340 345 350
<210> 124
<211> 15
<212> PRT
<213> 人工序列
<400> 124
Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr
1 5 10 15
<210> 125
<211> 15
<212> PRT
<213> 人工序列
<400> 125
Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe
1 5 10 15
<210> 126
<211> 15
<212> PRT
<213> 人工序列
<400> 126
Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr
1 5 10 15
<210> 127
<211> 10
<212> PRT
<213> 人工序列
<400> 127
Gly Ser Ser Gly Val Val Asn Pro Val Met
1 5 10
<210> 128
<211> 16
<212> PRT
<213> 人工序列
<400> 128
Asn Ala Pro Arg Ile Thr Phe Gly Gly Pro Ser Asp Ser Thr Gly Ser
1 5 10 15
<210> 129
<211> 15
<212> PRT
<213> 人工序列
<400> 129
Tyr Ile Arg Val Gly Ala Arg Lys Ser Ala Pro Leu Ile Glu Leu
1 5 10 15
<210> 130
<211> 15
<212> PRT
<213> 人工序列
<400> 130
Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile
1 5 10 15
<210> 131
<211> 15
<212> PRT
<213> 人工序列
<400> 131
Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala
1 5 10 15
<210> 132
<211> 12
<212> PRT
<213> 人工序列
<400> 132
Met Trp Leu Ser Tyr Phe Ile Ala Ser Phe Arg Leu
1 5 10
<210> 133
<211> 5
<212> PRT
<213> 人工序列
<400> 133
Ile Val Asp Glu Pro
1 5
<210> 134
<211> 12
<212> PRT
<213> 人工序列
<400> 134
Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro
1 5 10
<210> 135
<211> 13
<212> PRT
<213> 人工序列
<400> 135
Lys Thr Phe Pro Pro Thr Glu Pro Lys Lys Asp Lys Lys
1 5 10
<210> 136
<211> 19
<212> PRT
<213> 人工序列
<400> 136
Leu Gly Val Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe
1 5 10 15
Arg Val Tyr
<210> 137
<211> 15
<212> PRT
<213> 人工序列
<400> 137
Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr
1 5 10 15
<210> 138
<211> 10
<212> PRT
<213> 人工序列
<400> 138
Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr
1 5 10
<210> 139
<211> 15
<212> PRT
<213> 人工序列
<400> 139
Ala Gly Asn Gly Gly Asp Ala Ala Leu Ala Leu Leu Leu Leu Asp
1 5 10 15
<210> 140
<211> 11
<212> PRT
<213> 人工序列
<400> 140
Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser
1 5 10
<210> 141
<211> 10
<212> PRT
<213> 人工序列
<400> 141
Ala Asp Gln Leu Thr Pro Thr Trp Arg Val
1 5 10
<210> 142
<211> 10
<212> PRT
<213> 人工序列
<400> 142
Phe Ile Tyr Asn Lys Ile Val Asp Glu Pro
1 5 10
<210> 143
<211> 10
<212> PRT
<213> 人工序列
<400> 143
Lys Asn Pro Leu Leu Tyr Asp Ala Asn Tyr
1 5 10
<210> 144
<211> 11
<212> PRT
<213> 人工序列
<400> 144
Arg Pro Gln Gly Leu Pro Asn Asn Thr Ala Ser
1 5 10
<210> 145
<211> 23
<212> PRT
<213> 人工序列
<400> 145
Leu Ala Glu Ile Leu Gln Lys Asn Leu Ile Arg Gln Gly Thr Asp Tyr
1 5 10 15
Lys His Trp Pro Gln Ile Ala
20
<210> 146
<211> 10
<212> PRT
<213> 人工序列
<400> 146
Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu
1 5 10
<210> 147
<211> 15
<212> PRT
<213> 人工序列
<400> 147
Gly Ser Ser Gly Val Val Asn Pro Val Met Glu Pro Ile Tyr Asp
1 5 10 15
<210> 148
<211> 15
<212> PRT
<213> 人工序列
<400> 148
Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu
1 5 10 15
<210> 149
<211> 15
<212> PRT
<213> 人工序列
<400> 149
Ala Leu Pro Gln Arg Gln Lys Lys Gln Gln Thr Val Thr Leu Leu
1 5 10 15
<210> 150
<211> 10
<212> PRT
<213> 人工序列
<400> 150
Gly Ser Lys Ser Pro Ile Gln Tyr Ile Asp
1 5 10
<210> 151
<211> 14
<212> PRT
<213> 人工序列
<400> 151
Asp Phe Leu Glu Tyr His Asp Val Arg Val Val Leu Asp Phe
1 5 10
<210> 152
<211> 10
<212> PRT
<213> 人工序列
<400> 152
Gly Ile Asn Ala Ser Val Val Asn Ile Gln
1 5 10
<210> 153
<211> 10
<212> PRT
<213> 人工序列
<400> 153
Gln Phe Ala Pro Ser Ala Ser Ala Phe Phe
1 5 10
<210> 154
<211> 10
<212> PRT
<213> 人工序列
<400> 154
Pro Ser Gly Thr Trp Leu Thr Tyr Thr Gly
1 5 10
<210> 155
<211> 5
<212> PRT
<213> 人工序列
<400> 155
Glu Leu Asp Lys Tyr
1 5
<210> 156
<211> 10
<212> PRT
<213> 人工序列
<400> 156
Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val
1 5 10
<210> 157
<211> 15
<212> PRT
<213> 人工序列
<400> 157
Lys Ala Tyr Asn Val Thr Gln Ala Phe Gly Arg Arg Gly Pro Glu
1 5 10 15
<210> 158
<211> 10
<212> PRT
<213> 人工序列
<400> 158
Gly Thr Asn Thr Ser Asn Gln Val Ala Val
1 5 10
<210> 159
<211> 15
<212> PRT
<213> 人工序列
<400> 159
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr
1 5 10 15
<210> 160
<211> 10
<212> PRT
<213> 人工序列
<400> 160
Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr
1 5 10
<210> 161
<211> 15
<212> PRT
<213> 人工序列
<400> 161
Met Phe His Leu Val Asp Phe Gln Val Thr Ile Ala Glu Ile Leu
1 5 10 15
<210> 162
<211> 10
<212> PRT
<213> 人工序列
<400> 162
Met Lys Asp Leu Ser Pro Arg Trp Tyr Phe
1 5 10
<210> 163
<211> 10
<212> PRT
<213> 人工序列
<400> 163
Asp Ala Ala Leu Ala Leu Leu Leu Leu Asp
1 5 10
Claims (41)
1.一种蛋白质容器,其特征在于,其包括支持在不同位点处同时插入四条以上的外源多氨基酸序列的稳定蛋白质结构。
2.根据权利要求1所述的蛋白质容器,其特征在于,其包括与SEQ ID NO:1为至少90%同一性的氨基酸序列。
3.根据权利要求1所述的蛋白质容器,其特征在于,其包括与SEQ ID NO:3为至少90%同一性的氨基酸序列。
4.根据权利要求1所述的蛋白质容器,其特征在于,其包括与SEQ ID NO:77为至少90%同一性的氨基酸序列。
5.根据权利要求1至4中任一项所述的蛋白质容器,其特征在于,其在朝向外部环境的蛋白质环中具有用于外源多氨基酸序列的插入位点。
6.根据权利要求1至5中任一项所述的蛋白质容器,其特征在于,外源多氨基酸序列的同时插入不干扰容器蛋白的生产条件。
7.根据权利要求2至4中任一项所述的蛋白质容器,其特征在于,其同时包含外源多氨基酸序列,用于疫苗组合物、用于诊断、或用于实验室试剂的开发。
8.根据权利要求2至4中任一项所述的蛋白质容器,其特征在于,所述外源多氨基酸序列在同时插入至所述蛋白质容器的蛋白质环的情况下不丧失它们的免疫原性特性。
9.根据权利要求2所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ IDNO:13、SEQ ID NO:14、SEQ ID NO:15和SEQ ID NO:16。
10.根据权利要求9所述的蛋白质容器,其特征在于,其包括SEQ ID NO:18中所示的氨基酸序列。
11.根据权利要求3所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQID NO:27、SEQ ID NO:28和SEQ ID NO:29。
12.根据权利要求11所述的蛋白质容器,其特征在于,其包括SEQ ID nO:20中所示的氨基酸序列。
13.根据权利要求3所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:30的多个拷贝。
14.根据权利要求13所述的蛋白质容器,其特征在于,其包括SEQ ID nO.31中所示的氨基酸序列。
15.根据权利要求3所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39和SEQ ID NO:40。
16.根据权利要求15所述的蛋白质容器,其特征在于,其包括SEQ ID nO:33中所示的氨基酸序列。
17.根据权利要求3所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:41、SEQ ID NO:42、SEQ ID NO:43和SEQ ID NO:44。
18.根据权利要求17所述的蛋白质容器,其特征在于,其包括SEQ ID NO:45中所示的氨基酸序列。
19.根据权利要求3所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:47、SEQ ID NO:48、SEQ ID NO:49和SEQ ID NO:50。
20.根据权利要求19所述的蛋白质容器,其特征在于,其包括SEQ ID NO:.51中所示的氨基酸序列。
21.根据权利要求3所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:95和SEQ ID NO:96。
22.根据权利要求21所述的蛋白质容器,其特征在于,其包括SEQ ID NO:.64中所示的氨基酸序列。
23.根据权利要求3所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:70、SEQID NO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ ID NO:74和SEQ ID NO:97。
24.根据权利要求23所述的蛋白质容器,其特征在于,其包括SEQ ID NO:.75中所示的氨基酸序列。
25.根据权利要求4所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ ID NO:84、SEQID NO:85、SEQ ID NO:86、SEQ ID NO:87和SEQ ID NO:98。
26.根据权利要求25所述的蛋白质容器,其特征在于,其包括SEQ ID NO:.88中所示的氨基酸序列。
27.根据权利要求4所述的蛋白质容器,其特征在于,其同时包括外源多氨基酸序列SEQID NO:7、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:15、SEQID NO:16、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:94和SEQ ID NO:99。
28.根据权利要求27所述的蛋白质容器,其特征在于,其包括SEQ ID NO:.90中所示的氨基酸序列。
29.根据权利要求4所述的蛋白质容器,其特征在于,其同时包括如SEQ ID NO:100、124、125和126中所限定的外源多氨基酸序列;或者,同时包括如SEQ ID NO:101、127、128、129、130、131、132、133、134和135中所限定的外源多氨基酸序列;或者,同时包括如SEQ IDNO:136、137、138、139、140、141、142中所限定的外源多氨基酸序列;或者,同时包括如SEQID NO:129、133、135、137、140、141、142、143、144、146、147、和148中所限定的外源多氨基酸序列;或者,同时包括如SEQ ID NO:103、149、150、151、152、153、154、155中所限定的外源多氨基酸序列;或者,同时包括如SEQ ID NO:104、156、157、158、159、160、161、162和163中所限定的外源多氨基酸序列;或者,同时包括如SEQ ID NO:136、139、140、141、142、143、144、146和147中所限定的外源多氨基酸序列。
30.根据权利要求29所述的蛋白质容器,其特征在于,其包括SEQ ID NO:.116-123中所示的任意氨基酸序列。
31.一种多核苷酸,其特征在于,其包括SEQ ID NO:2、4、78、17、19、32、34、46、52、63、76、89、91、108-115的任一者及其简并序列,能够分别地产生由SEQ ID NO:1、3、77、18、20、31、33、45、51、64、75、88、90、116-123所限定的多肽。
32.一种载体,其特征在于,其包括如权利要求31中所限定的多核苷酸。
33.一种表达盒,其特征在于,其包括如权利要求31中所限定的多核苷酸。
34.一种细胞,其特征在于,其包括如权利要求32中所限定的载体或如权利要求33中所限定的表达盒。
35.一种生产蛋白质容器的方法,其特征在于,其将如权利要求31中所限定的多核苷酸引入感兴趣的感受态细胞;进行感受态细胞的培养并进行含有选择的外源多氨基酸的容器蛋白的分离。
36.根据权利要求35所述的生产蛋白质容器的方法,其特征在于,其免受各种外源多氨基酸序列的插入的干扰。
37.一种病原体识别或体外疾病诊断的方法,其特征在于,其使用如权利要求1至30中任一项所限定的容器蛋白。
38.根据权利要求37所述的病原体识别或疾病诊断的方法,其特征在于,其促进恰加斯病、狂犬病、百日咳、黄热病、奥罗普切病毒病毒感染、马雅罗病毒感染、IgE超敏反应、屋尘螨过敏、或COVID-19的诊断。
39.如权利要求1至30中任一项所限定的蛋白质容器的用途,其特征在于,其为实验室试剂。
40.如权利要求1至30中任一项所限定的蛋白质容器的用途,其特征在于,其为用于针对恰加斯病、狂犬病、百日咳、黄热病、由奥罗普切病毒、马雅罗病毒的感染、对IgE的超敏反应、对屋尘螨的过敏或COVID-19的免疫的疫苗组合物的生产。
41.一种诊断试剂盒,其特征在于,其包括如权利要求1至30中任一项所限定的蛋白质容器。
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PCT/BR2020/050341 WO2021035325A1 (pt) | 2019-08-27 | 2020-08-27 | Receptáculo proteico, polinucleotideo, vetor, cassete de expressão, célula, método para produção do receptáculo, método de identificação de patógenos ou de diagnóstico de doenças, uso do receptáculo, e, kit diagnóstico |
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CN114832099B (zh) * | 2022-04-08 | 2023-11-28 | 国科宁波生命与健康产业研究院 | 一种用于治疗SARS-CoV-2变异毒株感染的多肽制剂 |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5625048A (en) | 1994-11-10 | 1997-04-29 | The Regents Of The University Of California | Modified green fluorescent proteins |
GB9504446D0 (en) | 1995-03-06 | 1995-04-26 | Medical Res Council | Improvements in or relating to gene expression |
US5874304A (en) | 1996-01-18 | 1999-02-23 | University Of Florida Research Foundation, Inc. | Humanized green fluorescent protein genes and methods |
US5804387A (en) | 1996-02-01 | 1998-09-08 | The Board Of Trustees Of The Leland Stanford Junior University | FACS-optimized mutants of the green fluorescent protein (GFP) |
US6096865A (en) | 1996-05-06 | 2000-08-01 | Amgen Inc. | Mutants of the green fluorescent protein having improved fluorescent properties at 37° |
US6027881A (en) | 1996-05-08 | 2000-02-22 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Mutant Aequorea victoria fluorescent proteins having increased cellular fluorescence |
US6124128A (en) | 1996-08-16 | 2000-09-26 | The Regents Of The University Of California | Long wavelength engineered fluorescent proteins |
US6025485A (en) | 1997-02-14 | 2000-02-15 | Arcaris, Inc. | Methods and compositions for peptide libraries displayed on light-emitting scaffolds |
US7090976B2 (en) | 1999-11-10 | 2006-08-15 | Rigel Pharmaceuticals, Inc. | Methods and compositions comprising Renilla GFP |
US7297482B2 (en) | 1998-10-08 | 2007-11-20 | Rigel Pharmaceuticals, Inc. | Structurally biased random peptide libraries based on different scaffolds |
US6936421B2 (en) * | 1998-10-08 | 2005-08-30 | Rigel Pharmaceuticals, Inc. | Structurally biased random peptide libraries based on different scaffolds |
US6180343B1 (en) | 1998-10-08 | 2001-01-30 | Rigel Pharmaceuticals, Inc. | Green fluorescent protein fusions with random peptides |
AU1482101A (en) | 1999-11-10 | 2001-06-06 | Rigel Pharmaceuticals, Inc. | Methods and compositions comprising renilla gfp |
WO2004005322A2 (en) | 2002-07-10 | 2004-01-15 | Stratagene | Humanized renilla reniformis green fluorescent protein as a scaffold |
US20100137158A1 (en) * | 2008-10-31 | 2010-06-03 | Wisconsin Alumni Research Foundation | GFABS: GFP-based biosensors possessing the binding properties of antibodies |
CN104619726B (zh) | 2012-03-23 | 2018-05-18 | 苏州鲲鹏生物技术有限公司 | 由超折叠绿色荧光蛋白构成的融合蛋白及其用途 |
WO2014144583A2 (en) * | 2013-03-15 | 2014-09-18 | Northwestern University | Methods for cell- free protein synthesis |
CN106591343B (zh) * | 2016-11-29 | 2020-02-18 | 湖北大学 | 一种超折叠绿色荧光蛋白介导异源蛋白在大肠杆菌中分泌表达方法 |
CN106986922B (zh) | 2017-04-14 | 2020-03-06 | 江南大学 | 一种自组装双亲短肽及其应用 |
CN107703219B (zh) | 2017-07-28 | 2019-09-27 | 浙江大学 | 基于CILLC-MS的评价GFP基因转染对hPMSCs代谢组学影响的方法 |
CN108220313A (zh) | 2018-01-12 | 2018-06-29 | 辽宁科技大学 | 一种绿色荧光蛋白的融合表达方法 |
CN108192904B (zh) | 2018-01-29 | 2019-10-08 | 怀化学院 | 一种穿膜荧光蛋白及其编码基因与应用 |
CN108303539B (zh) | 2018-01-31 | 2020-08-11 | 刘双萍 | 一种乳腺癌细胞检测生物试剂及应用 |
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