CN1268745C

CN1268745C - B组链球菌抗原

Info

Publication number: CN1268745C
Application number: CNB998052485A
Authority: CN
Inventors: B·R·布罗多伊尔; C·里奥克斯; M·波耶尔; I·查勒波伊斯; J·哈梅尔; D·马丁
Original assignee: Biochem Pharma Inc
Current assignee: ID BIOMEDICAL CORP; Shire Canada Inc
Priority date: 1998-02-20
Filing date: 1999-02-17
Publication date: 2006-08-09
Anticipated expiration: 2019-02-17
Also published as: US20030228323A1; DE69934299D1; ATE347600T1; CZ20003054A3; US20030031682A1; IL190018A0; EP1757697A2; CA2321106C; NO20004161L; ES2540281T3; HU228497B1; IL137921A; KR20010034518A; NO20004161D0; US20110182923A1; EP1054971A2; US7914794B2; EP1054971B1; IL190018A; AU2505999A

Abstract

本发明公开了B组链球菌(GBS)蛋白质和其编码多核苷酸。所述蛋白质是有抗原性的，所以是预防或治疗动物链球菌感染的有用疫苗成分。还公开了制备所述蛋白抗原的重组方法以及用于检测链球菌感染的诊断测试。

Description

B组链球菌抗原

发明领域

本发明涉及抗原，更特别地涉及用作治疗和/或预防的疫苗成分的B组链球菌(GBS)细菌病原体的蛋白质抗原。

发明背景

链球菌是革兰氏阳性细菌，它们按它们细胞表面上发现的A组至0组具体碳水化合物抗原来划分。链球菌组进一步通过具体类型荚膜多糖抗原来区分。对于B组链球菌(GBS)鉴定了几种血清型：Ia，Ib，II，III，IV，V，VI，VIIh VIII。GBS还包括已知为“C-蛋白质”(α，β，γ和δ)，其中一些已经被克隆出来。

尽管GBS是正常人阴道和结肠菌丛的共同成分，但是该病原体长期以来一直被认为是新生期脓毒症，脑膜炎，婴儿脑膜炎后遗症，产后子宫内膜炎以及牛奶场放牧人乳腺炎的主要病因。暴露给GBS的待产妇有产后感染的危险并且可能在孩子通过产道时将感染转移给她们的孩子。尽管微生物对抗生素敏感，但是由于新生期脓毒症和婴儿脑膜炎高的发生比例和快的发生速度而导致高的发病率和死亡率。

为了发现保护人们不受GBS感染的疫苗，研究转向特异型抗原。令人遗憾的是，证明了这些多糖在人体内具有不好的免疫原性并且限制于这些多糖发源的特殊血清型。此外，荚膜多糖激发T细胞独立响应，即没有IgG产生。结果荚膜多糖抗原不适合作为保护抗GBS感染的疫苗成分。

其它人观注C-蛋白β抗原，其被证明在小鼠和兔模型中有免疫原性。发现该性质不适合作为人疫苗，因为其与该亲和性相互作用和与人IgA的Fc区的非免疫原性方式的不期望的性质。C-蛋白α抗原在负责大多数GBS介导的疾病的血清型GBS的III型血清型中很少，因此作为疫苗成分几乎没有用途。

因此，对于可以用作预防和/或治疗GBS感染的疫苗成分的GBS抗原还有没有满足的要求。

发明概述

根据一方面，本发明提供编码与包括选自下面的一个序列的第二多肽至少70％一致性的多肽的分离的多核苷酸：

SEQ ID NO：2，SEQ ID NO：3，SEQ ID NO：4，SEQ ID NO：5，

SEQ ID NO：6，SEQ ID NO：8，SEQ ID NO：9，SEQ ID NO：10，

SEQ ID NO：11，SEQ ID NO：12，SEQ ID NO：14，SEQ ID NO：15，

SEQ ID NO：16，SEQ ID NO：17，SEQ ID NO：18，SEQ ID NO：19，

SEQ ID NO：20，SEQ ID NO：21，SEQ ID NO：23，SEQ ID NO：24，

SEQ ID NO：25，SEQ ID NO：26，SEQ ID NO：28，SEQ ID NO：29，

SEQ ID NO：30，SEQ ID NO：31，SEQ ID NO：33，SEQ ID NO：34，

SEQ ID NO：35，SEQ ID NO：36，SEQ ID NO：38，SEQ ID ND：39，

SEQ ID NO：40，SEQ ID NO：41和SEQ ID NO：44

或者其片段，类似物或衍生物。

在其它方面，提供包括操作性连接了表达调控区的本发明多核苷酸的载体，以及用所述载体转染的宿主细胞，和产生多肽的方法，包括在适合表达的条件下培养所述宿主细胞。

在另一方面，提供本发明多核苷酸编码的新的多肽。

附图的简要描述

图1a是克隆1的DNA序列(SEQ ID NO：1)与相应的可读框的氨基酸序列；

图1b是氨基酸序列SEQ ID NO：2；

图1c是氨基酸序列SEQ ID NO：3；

图1d是氨基酸序列SEQ ID NO：4；

图1e是氨基酸序列SEQ ID NO：5；

图1f是氨基酸序列SEQ ID NO：6；

图2a是克隆2的DNA序列(SEQ ID NO：7)与相应的可读框的氨基酸序列；

图2b是氨基酸序列SEQ ID NO：8；

图2c是氨基酸序列SEQ ID NO：9；

图2d是氨基酸序列SEQ ID NO：10；

图2e是氨基酸序列SEQ ID NO：11；

图2f是氨基酸序列SEQ ID NO：12；

图3a是克隆3的DNA序列(SEQ ID NO：13)与相应的可读框的氨基酸序列；

图3b是氨基酸序列SEQ ID NO：14；

图3c是氨基酸序列SEQ ID NO：15；

图3d是氨基酸序列SEQ ID NO：16；

图3e是氨基酸序列SEQ ID NO：17；

图3f是氨基酸序列SEQ ID NO：18；

图3g是氨基酸序列SEQ ID NO：19；

图3h是氨基酸序列SEQ ID NO：20；

图3i是氨基酸序列SEQ ID NO：21；

图4a是克隆4的DNA序列(SEQ ID NO：22)与相应的可读框的氨基酸序列；

图4b是氨基酸序列SEQ ID NO：23；

图4c是氨基酸序列SEQ ID NO：24；

图4d是氨基酸序列SEQ ID NO：25；

图4e是氨基酸序列SEQ ID NO：26；

图5a是克隆5的DNA序列(SEQ ID NO：27)与相应的可读框的氨基酸序列；

图5b是氨基酸序列SEQ ID NO：28；

图5c是氨基酸序列SEQ ID NO：29；

图5d是氨基酸序列SEQ ID NO：30；

图5e是氨基酸序列SEQ ID NO：31；

图6a是克隆6的DNA序列(SEQ ID NO：32)与相应的可读框的氨基酸序列；

图6b是氨基酸序列SEQ ID NO：33；

图6c是氨基酸序列SEQ ID NO：34；

图6d是氨基酸序列SEQ ID NO：35；

图6e是氨基酸序列SEQ ID NO：36；

图7a是克隆7的DNA序列(SEQ ID NO：37)；

图7b是氨基酸序列SEQ ID NO：38；

图7c是氨基酸序列SEQ ID NO：39；

图7d是氨基酸序列SEQ ID NO：40；

图7e是氨基酸序列SEQ ID NO：41；

图8是包括信号序列的克隆7的一部分的DNA序列(SEQ ID NO：42)；

图9是不包括信号序列的克隆7的一部分的DNA序列(SEQ ID NO：43)；

图9a是氨基酸序列SEQ ID NO：44；

图10代表来自用相应于SEQ ID NO：39的重组GBS蛋白质免疫的CD-1小鼠血清的抗-GBS ELISA效价的分布。

本发明的详细描述

本发明涉及B组链球菌(GBS)的新的抗原多肽，特征在于是选自下面的氨基酸序列：

SEQ ID NO：2，SEQ ID NO：3，SEQ ID NO：4，SEQ ID NO：5，

SEQ ID NO：6，SEQ ID NO：8，SEQ ID NO：9，SEQ ID NO：10，

SEQ ID NO：11，SEQ ID NO：12，SEQ ID NO：14，SEQ ID NO：15，

SEQ ID NO：16，SEQ ID NO：17，SEQ ID NO：18，SEQ ID NO：19，

SEQ ID NO：20，SEQ ID NO：21，SEQ ID NO：23，SEQ ID NO：24，

SEQ ID NO：25，SEQ ID NO：26，SEQ ID NO：28，SEQ ID NO：29，

SEQ ID NO：30，SEQ ID NO：31，SEQ ID NO：33，SEQ ID NO：34，

SEQ ID NO：35，SEQ ID NO：36，SEQ ID NO：38，SEQ ID NO：39，

SEQ ID NO：40，SEQ ID NO：41和SEQ ID NO：44

或者其片段，类似物或衍生物。

本发明的优选实施方案包括SEQ ID NO：39和SEQ ID NO：44。

本发明的进一步优选实施方案包括SEQ ID NO：39。

本发明的进一步优选实施方案包括SEQ ID NO：44。

如这里所使用的，本发明多肽的“片段”，“衍生物”或“类似物”包括其中一个或多个氨基酸残基被保守的或者不保守的氨基酸残基(优选保守的)取代并且可以是天然的或非天然的那些多肽。

本发明多肽的术语“片段”，“衍生物”或“类似物”包括添加，缺失，取代氨基酸的修饰的多肽，前提是这些多肽保持诱导免疫应答的能力。

术语“保守的氨基酸”是指一个或多个氨基酸被其它氨基酸取代，其中即使发生取代，给定抗原的抗原决定簇(包括其二级结构和亲水性质)也是完全或部分保守的。

例如，所述序列中一个或多个氨基酸残基可以被另一个相似极性的作为功能等价物起作用的氨基酸取代，导致沉默改变。所述序列中氨基酸的取代物可以选自该氨基酸所属于的种类其它成员。例如，非极性(疏水性)氨基酸包括丙氨酸，亮氨酸，异亮氨酸，缬氨酸，脯氨酸，苯丙氨酸，色氨酸和蛋氨酸。极性中性氨基酸包括甘氨酸，丝氨酸，苏氨酸，半胱氨酸，酪氨酸，天冬酰胺和谷氨酰胺。带正电荷(碱性)氨基酸包括精氨酸，赖氨酸和组氨酸。带负电荷(酸性)氨基酸包括天冬氨酸和谷氨酸。

优选地，本发明多肽的衍生物和类似物与图中图示说明的那些序列或者其片段具有大约70％的一致性。也就是说70％的残基相同。更优选地，多肽具有大于95％的同源性。在另一个优选的实施方案中，本发明多肽的衍生物和类似物具有少于大约20个氨基酸残基的取代，修饰或缺失，更优选地少于10个。优选的取代物是本领域已知为保守的那些，即被取代的残基具有相同的物理或化学性质，例如疏水性，大小，电荷或者官能团。

此外，在氨基酸区被发现是多态的情况下，可以预期改变一个或多个特殊氨基酸以更有效地模拟不同GBS株的不同表位。

还包括与改变多肽生物或药学性质的其它化合物，即聚乙二醇(PEG)融合以提高半寿期的多肽，易于纯化的前导或分泌氨基酸序列；前序列原和前序列；和多糖。

此外，本发明的多肽可以通过末端-NH₂酰化作用(例如通过乙酰化作用，或者硫代乙二醇酸酰胺化作用，末端羧酸(carbosy)酰胺化作用，例如与氨或者甲胺)而被修饰，以提供连接或键合载体或其它分子的稳定性，提高的疏水性。

还涉及所述多肽片段，类似物和衍生物的杂聚和同聚多肽多聚体。这些聚合物形式包括，例如，与交联剂例如亲和素/生物素，戊二醛或二甲基超亚胺酯(dimethyl-superimidate)交联的一种或多种多肽。这样的聚合物形式还包括包含通过DNA重组技术产生的多顺反子mRNAs制备的两个或多个串联的或者倒位的连续序列的多肽。优选地，本发明多肽的片段，类似物或衍生物包括至少一个抗原区，即至少一个表位。

为了实现抗原聚合物(即合成的多聚体)的形成，可以使用具有二卤代酰基，硝基芳基卤化物等等的多肽，其中试剂对于硫基是特异性的。因此，不同肽的两个巯基之间的连接可以是单键或者可以由至少两个，典型地至少4个，不多于16个，但是通常不多于14个碳原子的连接基团组成。

在具体的实施方案中，本发明的多肽片段，类似物和衍生物不含有蛋氨酸(Met)起始残基。优选地，多肽将不插入一个前导或分泌序列(信号序列)。根据已确定的分子生物学技术可以确定本发明多肽的信号部分。一般情况下，可以从GBS培养物分离所感兴趣的多肽并且接着测序确定成熟蛋白的初始残基，从而确定成熟多肽的序列。

根据另一方面，提供了包括与药学可接受载体稀释剂或佐剂混合的一种或多种本发明GBS多肽的疫苗组合物。

合适的佐剂包括油，即弗氏完全佐剂或不完全佐剂；盐，即AlK(SO₄)₂，AlNa(SO₄)₂，AlNH₄(SO₄)₂，Al(OH)₃，AlPO₄，二氧化硅，高岭土；皂草甙衍生物；碳多核苷酸，即多IC和多AU，还有解毒的霍乱毒素(CTB)和诱导粘膜免疫的大肠杆菌热不稳定毒素。优选的佐剂包括QuilA^TM，Alhydrogel^TM，和Adjuphos^TM。本发明的疫苗可以通过注射，快速灌注，鼻咽吸收，皮肤吸收，非经肠给药，或者含化或者口服给药。

本发明的疫苗组合物用于治疗或预防链球菌感染和/或链球菌感染介导的疾病和症状，特别是A组链球菌(化脓链球菌)，B组链球菌(GBS或无乳链球菌)，停乳链球菌，乳房链球菌，诺氏链球菌以及金黄色葡萄球菌。关于链球菌的一般信息参见Manual of ClinicalMicrobiology，P.R.Murray等，(1995，第六版，ASM出版社，华盛顿)。更特别地是B组链球菌，无乳链球菌。在具体的实施方案中，对有GBS感染危险的那些个体施用疫苗，所述个体是例如孕妇和婴儿脓毒症，脑膜炎和肺炎以及无免疫应答的个体，例如糖尿病，肝病或癌症的那些。疫苗也具有兽药用途，例如用于治疗上述细菌以及大肠杆菌介导的牛乳腺炎。

本发明的疫苗还可以用来制备用于治疗或预防链球菌感染和/或链球菌感染介导的疾病和症状的药物，所述链球菌特别是A组链球菌(化脓链球菌)，B组链球菌(GBS或无乳链球菌)，停乳链球菌，乳房链球菌，诺氏链球菌以及金黄色葡萄球菌。更特别地是B组链球菌，无乳链球菌。

疫苗组合物优选以0.001至100μg/kg(抗原/体重)，更优选地0.01至10μg/kg和最优选地0.1至1μg/kg的单位剂量形式，免疫之间大约1至12周间隔免疫1至3次，更优选地间隔1至6周。

根据另一方面，提供了编码特征在于氨基酸序列选自下组的B组链球菌(GBS)多肽的多核苷酸：

SEQ ID NO：2，SEQ ID NO：3，SEQ ID NO：4，SEQ ID NO：5，

SEQ ID NO：6，SEQ ID NO：8，SEQ ID NO：9，SEQ ID NO：10，

SEQ ID NO：11，SEQ ID NO：12，SEQ ID NO：14，SEQ ID NO：15，

SEQ ID NO：16，SEQ ID NO：17，SEQ ID NO：18，SEQ ID NO：19，

SEQ ID NO：20，SEQ ID NO：21，SEQ ID NO：23，SEQ ID NO：24，

SEQ ID NO：25，SEQ ID NO：26，SEQ ID NO：28，SEQ ID NO：29，

SEQ ID NO；30，SEQ ID NO：31，SEQ ID NO：33，SEQ ID NO：34，

SEQ ID NO：35，SEQ ID NO：36，SEQ ID NO：38，SEQ ID NO：39，

SEQ ID NO：40，SEQ ID NO：41和SEQ ID NO：44

或者其片段，类似物或衍生物。

优选的多核苷酸是在图1a(SEQ ID NO：1)，2a(SEQ ID NO：7)，3a(SEQ ID NO：13)，4a(SEQ ID NO：22)，5a(SEQ ID NO：27)，6a(SEQ ID NO：32)，7a(SEQ ID NO：37)，8(SEQ ID NO：42)和9(SEQ ID NO：43)中图示说明的那些，它们相应于编码本发明多肽的可读框。

优选的多核苷酸是在图1a(SEQ ID NO：1)，2a(SEQ ID NO：7)，3a(SEQ ID NO：13)，4a(SEQ ID NO：22)，5a(SEQ ID NO：27)，6a(SEQ ID NO：32)，7a(SEQ ID NO：37)，8(SEQ ID NO：42)和9(SEQ ID NO：43)中图示说明的那些，和它们的片段，类似物和衍生物。

更优选的本发明的多核苷酸是图7(SEQ ID NO：37)，8(SEQ ID NO：42)和9(SEQ ID NO：43)中图示说明的那些。

最优选的本发明的多核苷酸是图8(SEQ ID NO：42)和9(SEQ ID NO：43)中图示说明的那些。

要理解图中说明的多核苷酸序列可以用也编码本发明多肽的简并密码子改变。

由于核苷酸编码序列的简并性，本发明实施中也可以使用编码本发明基本上相同的多肽的其它多核苷酸序列。这些包括但不限于编码序列内相同氨基酸残基的不同密码子的取代而改变从而产生沉默变化的核苷酸序列。

因此，本发明进一步提供与上述多核苷酸序列杂交的多核苷酸(或者其互补序列)，序列之间具有50％，优选地具有至少70％一致性。更优选地，多核苷酸在严格条件下是可杂交的，即具有至少95％一致性，最优选地大于97％一致性。

能在严格条件下杂交是指核苷酸分子在标准条件下，例如高温和/或低盐含量下，退火生成第二核酸序列的至少一个区(或者作为cDNA，或者作为基因组DNA)或者生成其互补链，其趋向于不利于非互补核苷酸序列的杂交。合适的方法描述于Maniatis T.等，分子克隆：实验室手册，冷泉港实验室，1982，其在这里引作参考。

再一方面，可以在DNA免疫方法中使用编码本发明多肽的多核苷酸，或者其片段，类似物或衍生物。即，它们可以被插入到载体中，该载体在注射后是可复制和可表达的，从而体内产生抗原性多肽。例如于在真核细胞中起作用的CMV启动子控制下，多核苷酸可以插入到质粒载体中。优选地肌内注射载体。

根据另一方面，提供了通过重组技术通过在宿主细胞中表达编码所述多肽的多核苷酸并且回收表达的多肽产物而制备本发明多肽的方法。或者，可以根据已确定的化学合成技术合成本发明多肽，即寡肽的液相或固相合成，连接寡肽产生全长多肽(封闭连接)。

对于重组体生产，用编码多肽的载体转染宿主细胞，然后在经改变适合激活启动子，选择转化物或者扩增基因的营养培养基中培养。合适的载体是在选择的宿主内可存活且可复制的那些载体，包括染色体的，非染色体的和合成的DNA序列，例如细菌质粒，噬菌体DNA，杆状病毒，酵母质粒，质粒和噬菌体DNA组合产生的载体。所述多肽序列可以使用限制酶在合适的位点插入载体中，这样其操作连接包括启动子，核糖体结合位点(共有区或核糖体结合序列)，和任选地操纵基因(调控元件)的表达调控区。人们可以根据已确定的分子生物学原理(Sambrook等，分子克隆：实验室手册，第二版，冷泉港实验室，纽约，1989，其在这里引作参考)选择适合给定宿主和载体的表达调控区的各成分。合适的启动子包括但不限于LTR或SV40启动子，大肠杆菌lac，tac或启动子和噬菌体λP_L启动子。载体优选插入复制起点以及选择标记，即氨苄青霉素抗性基因。合适的细菌载体包括pET，pQE70，pQE60，pQE-9，pbs，pD10phagescript，psiX174，pbluescriptSK，pbsks，pNH8A，pNH16a，pNH18A，pNH46A，ptrc99a，pKK223-3，pKK233-3，pDR540，pRIT5和真核载体pBlueBacIII，pWLNEO，pSV2CAT，pOG44，pXT1，pSG，pSVK3，pBPV，pMSG和pSVL。宿主细胞可以是细菌，即大肠杆菌，枯草芽孢杆菌，链霉菌属；真菌，即黑曲霉，构巢曲霉；酵母，即糖酵母属或者真核的，即CHO，COS。

在培养基中表达多肽时，一般通过离心收集细胞，然后通过物理或化学方法破碎(如果表达的多肽没有分泌到培养基中)，留下得到的粗提取物以分离感兴趣的多肽。从培养基或溶解物中纯化多肽可以根据多肽的性质通过已确定的技术进行，即利用硫酸铵或乙醇沉淀，酸提取，阴离子或阳离子交换层析，磷酸纤维素层析，疏水作用层析，羟基磷灰石层析和凝集素层析。可以应用HPLC实现最后的纯化。

多肽可以在有或没有前导或分泌序列下被表达。在前一种情况下，可以使用翻译后处理去除前导序列(参见US4431739；4425437；和4338397，这里引作参考)或者可以化学去除前导序列接着纯化表达的多肽。

根据又一方面，本发明的GBS多肽可以在诊断链球菌感染特别是GBS感染的诊断测定中使用。几种诊断方法是可能的，例如检测生物样品中的链球菌生物，可以进行下面的方法：

a)从患者获得生物样品；

b)培养与本发明GBS多肽反应的抗体或者其片段和生物样品，形成混合物；和

c)检测混合物中特异性结合的抗体或者结合的片段，这表明链球菌的存在。

或者，可以如下进行检测含有或者怀疑含有所述抗体的生物样品中对链球菌抗原特异性的抗体的方法：

a)从患者分离生物样品；

b)培养一种或多种本发明GBS多肽或者其片段和生物样品，形成混合物；和

c)检测混合物中特异性结合的抗原或者结合的片段，这表明链球菌特异性抗体的存在。

本领域技术人员会理解可以以几种形式进行诊断测定，包括免疫测定，例如酶联免疫吸附测定(ELISA)，放射免疫测定或者乳胶凝聚试验，特别是测定生物体内是否存在对所述蛋白质有特异性的抗体。

编码本发明多肽的DNA序列也可以用来设计用于检测怀疑含有链球菌的生物样品中链球菌的存在。本发明的检测方法包括：

a)从患者分离生物样品；

b)培养一种或多种具有编码本发明多肽的DNA序列或者其片段的DNA探针和生物样品，形成混合物；和

c)检测混合物中特异性结合的DNA探针，这表明链球菌的存在。

本发明的DNA探针也可以用来检测样品中的循环链球菌，即GBS核酸，例如使用聚合酶链反应，作为诊断链球菌感染的方法。所述探针可以应用常规技术合成和可以固定在固相上，或者可以用可检测的标记物标记。用于本申请的优选的DNA探针是具有与本发明GBS多肽的至少6个连续的核苷酸互补的序列的寡聚物。

检测患者体内链球菌的另一种诊断方法包括：

a)用可检测的标记物标记与本发明多肽或者其片段反应的抗体；

b)对患者施用标记的抗体或者标记的片段；和

c)检测患者体内特异性结合的标记的抗体或者标记的片段，这表明链球菌的存在。

本发明的再一方面是本发明的多肽作为用于产生用于诊断和特别是用于治疗链球菌感染的特异性抗体的免疫原的用途。可以使用适当的筛选方法确定合适的抗体，例如通过在试验模型中测定特定抗体对于抗链球菌感染的被动免疫的能力。动物模型的一个实施例是本申请实施例中描述的小鼠模型。所述抗体可以是整个抗体或者是其抗原结合片段，并且可以一般属于任何免疫球蛋白种类。所述抗体或片段可以是动物来源的，特别是哺乳动物源，更特别地是小鼠，大鼠或者人源。其可以是天然抗体或者其片段，或者如果期望，可以是重组体抗体或抗体片段。术语重组体抗体或抗体片段指应用分子生物学技术产生的抗体或抗体片段。所述抗体或抗体片段可以是多克隆抗体，或者优选地，单克隆抗体。其可以对多个与GBS多肽相关的表位是特异性的，但是优选对于一个表位是特异性的。

实施例1致死量B组链球菌(GBS)感染的小鼠模型

GBS感染的小鼠模型详细描述于Lancefield等(J.Exp.Med.142：165-179，1975)。对GBS株C388/90(1990年从加拿大喔太华的Children’sHospital of Eastern Ontario脑膜炎患者的脑脊液获得的临床分离物)和NCS246(National Center for Streptococcus，ProvincialLaboratory of Public Health for Northern Alberta，Edmonton，加拿大)分别血清型测定为Ia/c型和II/R型。

为了提高它们的致病力，如前所述(Lancefield等J.Exp.Med.142：165-179，1975)连续在小鼠中传代GBS株C388/90(血清型Ia/c)和NCS246(血清型II/R)。简要地说，使用从感染小鼠的血液或脾获得的在Todd-Hewitt肉汤中传代培养物的系列稀释物腹膜内接种来监测致病力的提高。最后传代后，使用感染的血样接种Todd-Hewitt肉汤。在37℃下7％CO₂下培养2小时后，向培养物加入终浓度10％(v/v)的甘油。然后将培养物分成等份并且在-80℃下保存，用于GBS攻击实验。测定这些冷冻的样品中存在的GBS的cfu数。对于GBS株C388/90和NCS246分别测定100％杀死(LD100)18周龄小鼠所必须的细菌浓度是3.5×10⁵和1.1×10⁵，这相应于肉汤菌株的致病力的显著增加。事实上，这两种菌株传代之前记录的LD100大于10⁹cfu。

在细菌攻击中，使用Todd-Hewitt肉汤将新解冻的致病GBS株等份调节到合适的细菌浓度并且对每一只雌性CD-1小鼠腹膜内注射1毫升。用于被动保护实验的小鼠是6-8周龄，而用于主动保护实验的小鼠在受攻击时大约18周龄。对所有的接种体证实菌落数。在攻击后头48小时每天4次观察动物的任何感染症状，接着下面的12天每天观察。在该时期最后，从生存者获得血样并且在-20℃下冷冻。培养从受攻击存活的每一只小鼠获得脾以鉴定所有存留的GBS。

实施例2用甲醛杀死的GBS全细胞免疫和保护小鼠

根据Lancefield等(J.Exp.Med.142：165-179，1975)描述的方法制备甲醛杀死的GBS全细胞。简要地说，将GBS株在绵羊血琼脂平板(Quelab Laboratories，Montreal，加拿大)上过夜培养物在PBS缓冲液(磷酸盐缓冲盐水，pH7.2)中清洗两次，调节至大约3×10⁹cfu/ml，并且在含有0.3％(v/v)甲醛的PBS中培养过夜。用PBS清洗杀死的GBS缓冲液并且在-80℃下冷冻保存。

以两周间隔，使用0.1毫升甲醛杀死的GBS株C388/900细胞(-6×10⁷GBS)或者用于对照组的0.1毫升PBS，对6-8周龄CD-1雌性小鼠(Charles River，St-Constant，Quebec，加拿大)皮下注射三次。在免疫的前一天，向这些制剂中加入0.14毫克或0.21毫克Al终浓度的Alhydrogel^TM(Superfos Biosetor，Frederikssund，Denmark)，并且在4℃搅拌下培养过夜。在免疫程序开始前和在最后注射后两周从每一只小鼠获得血清样品。血清在-20℃下冷冻。

第三次注射后1星期用1.5×10⁴cfu的GBS株C388/90(Ia/c)攻击注射PBS的每一个对照组中的8只小鼠和用甲醛杀死的全细胞GBS株C388/90(Ia/c)免疫的组。用甲醛杀死的GBS全细胞免疫的所有小鼠在同种攻击中存活，而在攻击后5天内，注射PBS的8只小鼠只有4只存活。为了提高对照组中的死亡率，在细菌攻击时必须根据小鼠年龄调节细菌悬浮液。在下面的攻击实验中，当小鼠大于15周龄时，细菌接种物的浓度提高到3.0×10⁵和2.5×10⁶cfu之间。

表1用甲醛杀死的GBS全细胞免疫CD1小鼠并且接着同种攻击(菌株C388/90(Ia/c))和异种攻击(菌株NCS246(II/R))

用于免疫的抗原制剂	细菌攻击后14天存活小鼠的数目(存活百分率％)
	细菌攻击后14天存活小鼠的数目(存活百分率％)		同种攻击：菌株C388/90(Ia/c)	异种攻击：菌株NCS246(II/R)
	第一次感染			异种攻击：菌株NCS246(II/R)
甲醛杀死的GBSC388/90(Ia/c)²细胞株	第一次感染			8/8(100)³	n.d.⁵
甲醛杀死的GBSC388/90(Ia/c)²细胞株	对照PBS	4/8(50)	n.d.	8/8(100)³	n.d.⁵
第二次感染			n.d.
第二次感染			甲醛杀死的GBSC388/90(Ia/c)细胞株	6/6(100)⁴	0/6(0)⁶
对照PBS	2/6(33)	0/6(0)	甲醛杀死的GBSC388/90(Ia/c)细胞株	6/6(100)⁴	0/6(0)⁶

¹使用终浓度是0.14毫克或0.21毫克Al的alhydrogel^TM；

²大约6×10⁷cfu；

³用调节到1.5×10⁴cfu的含有GBS C388/90(Ia/c)悬浮液的1毫升Todd-Hewitt培养基腹膜内攻击；

⁴用调节到2.1×10⁶cfu的含有GBS C388/90(Ia/c)悬浮液的1毫升Todd-Hewitt培养基腹膜内攻击；

⁵没有做；

⁶用调节到1.2×10⁵cfu的含有GBS NCS246(II/R)悬浮液的1毫升Todd-Hewitt培养基腹膜内攻击。

在另一项实验中，用PBS注射一组12只相应于对照组的小鼠，而用甲醛杀死的GBSC388/90(Ia/c)全细胞株免疫第二组12只小鼠。用2.1×10⁶cfu的GBSC388/90(Ia/c)株攻击这两组的每一个组的6只小鼠(表I)。第一个攻击实验中，所有用GBSC388/90(Ia/c)株免疫的小鼠在同种攻击中存活。注射PBS的6中小鼠中只有2只在感染中存活。

两个组中的剩下的6只然后在一周后证明该抗原制剂是否带来抗菌株NCS246(II/R)的交叉保护性，其产生血清学特性被膜。用第二GBS菌株感染的小鼠没有一只在感染中存活。后一种结果表明甲醛杀死的菌株C388/90诱导的保护性免疫应答的大多数抗荚膜多糖，这只限于特殊血清型的菌株。这些结果清楚地表明该特定感染模型可以有效地用于研究接种带来的保护作用。

实施例3用甲醛杀死的GBS全细胞免疫兔和小鼠的被动免疫保护

用甲醛杀死的GBS菌株C388/90(Ia/c)细胞免疫新西兰兔(2.5公斤，Charles River，St.Constant，Quebec，加拿大)，获得超免疫血清。以三星期间隔用大约1.5×10⁹cfu甲醛杀死的GBS菌株C388/90(Ia/c)全细胞对该兔皮下注射三次。弗氏完全佐剂(GibcoBRL LifeTechnologies，Grand Island，纽约)用作第一次免疫的佐剂，弗氏不完全佐剂(GibcoBRL)用于下面的两次注射。在免疫方案开始之前和在最后注射后2星期取血清样品。血清在-20℃下冷冻。

也评价了该特定兔超免疫血清对被动保护小鼠抗GBS致命感染的能力。攻击前18小时用15或25μL超免疫兔血清对小鼠腹膜内注射，被保护的5只小鼠中有4只抗感染(80％)。相比之下，用PBS或用脑膜炎外膜制剂免疫的兔获得的血清注射的对照组的小鼠存活率低于20％。该结果清楚地表明用杀死的GBS细胞免疫另一种动物物种可以诱导产生可以被动保护小鼠的抗体。该试剂也可以用来表征克隆。

表2用甲醛杀死的B组全链球菌(菌株C388/90(Ia/c))抗原制剂免疫后获得的兔血清带来的对CD-1小鼠的被动保护

组	GBS菌株C388/90(Ia/c)²细菌攻击后14天存活小鼠数	存活率(％)
组	GBS菌株C388/90(Ia/c)²细菌攻击后14天存活小鼠数	存活率(％)	兔超免疫血清²-25μl	4/5	80
兔超免疫血清²-15μl	4/5	80	兔超免疫血清²-25μl	4/5	80
兔超免疫血清²-15μl	4/5	80	对照兔血清-25μl	1/5	20
对照PBS	1/10	10	对照兔血清-25μl	1/5	20

¹弗氏完全佐剂用于第一次免疫，弗氏不完全佐剂用于下面的两次注射；

²用含有调节到2×10⁴cfu的GBS C388/90(Ia/c)的1毫升Todd-Hewitt培养基腹膜内攻击。

实施例4His.Tag-GBS融合蛋白的重组制备

使用包含分别加入限制酶切位点BglII(AGATCT)和HindIII(AAGCTT)的碱基延伸的寡聚物通过PCR(DNA Thermal Cycler GeneAmpPCT system2400 Perkin Elmer，San Jose，CA)从GBS菌株C388/90(Ia/c)的基因组DNA扩增GBS基因的编码区。使用购自Qiagen(Chatsworth，CA)的QiaexII凝胶提取试剂盒用琼脂糖凝胶纯化PCR产物，用限制酶BglII和HindIII(Pharmacia Canada Inc Baie d’Urfa，加拿大)消化，在乙醇沉淀之前用苯酚：氯仿提取。用限制酶BglII和HindIII消化包含硫氧还蛋白-His.Tag序列的pET-32b(+)载体(Novagen，Madison，WI)，用苯酚：氯仿提取，然后乙醇沉淀之。BglII-HindIII基因组DNA片段连接BglII-HindIII pET-32b(+)载体，产生其基因在T7启动子控制下的硫氧还蛋白-His.Tag-GBS融合蛋白的编码序列。根据Simanis的方法(Hanahan，D.DNA克隆，1985，D.M.Glover(编著)，pp.109-135)，将连接产物转化到大肠杆菌菌株XLIBlue MRF’(Δ(mcrA)183Δ(mcrCB-hsdSMR-mrr)173 endA1 supE44 thi-1recA1 gyrA96 relA1 lac(F’proAB lacI^qZΔM15Tn10(Tet^r))^c)(Stratagene，La Jolla，CA)中。使用Qiagen试剂盒(Qiagen，Chatsworth，CA)纯化重组pET质粒，并且通过DNA测序(Taq Dye，DeoxyTerminator Cycle Sequencing kit，ABI，Foster City，CA)证实所述DNA插入片段的核苷酸序列。通过电穿孔(Gene PulserII apparatus，BIO-RAD Labs，Mississauga，加拿大)将重组pET质粒转化到大肠杆菌菌株AD494(DE3)(Δara-leu7697ΔlacX74ΔphoA pvuII phoRΔmalF3F’(lacI⁺(lacI^q)pro)trxB::Kan(DE3))(Novagen，Madison，WI)k。在该大肠杆菌菌株中，其基因处于lac启动子控制下的T7RNA聚合酶(存在于λDE3原噬菌体上)特异性识别控制所述融合蛋白表达的T7启动子，其中所述lac启动子由异丙基-β-D-硫代吡喃半乳糖(IPTG)诱导。

250rpm搅拌下在37℃下，在每毫升含有100μg氨苄青霉素(Sigma-Aldrich加拿大有限公司，Oakville，加拿大)的LB肉汤(蛋白胨10g/L，酵母提取物5g/L，NaCl 10g/L)中培养转化体AD494(DE3)/rpET，直到A₆₀₀达到0.6的值。为了诱导硫氧还蛋白-His.Tag-GBS融合蛋白的产生，在IPTG存在下以1mM终浓度将细胞再培养2小时。离心收集细菌细胞。

IPTG诱导2小时下AD494(DE3)/rpET32产生的重组融合蛋白部分以不溶的包函体获得，通过分离不溶的团聚体从内源大肠杆菌蛋白质将其纯化(Gerlach，G.F.等1992，Infect.Immun.60：892)。从500毫升培养物诱导的细胞悬浮于20毫升25％蔗糖-50mM Tris-HCl缓冲液(pH8.0)并在-70℃下冷冻。通过加入5毫升250mM Tris-HCl缓冲液(pH8.0)中的溶菌酶溶液(10mg/ml)，接着在冰上温育10-15分钟，并且加入150毫升洗涤剂混合物(5份20mM Tris-HCl缓冲液(pH7.4)-300mM NaCl-2％脱氧胆酸-2％Nonidet P-40和4份100mM Tris-HCl缓冲液(pH8)-50mM EDTA-2％Triton X-100)，接着在冰上温育5分钟，实现解冻的悬浮液的溶解。超声处理后，通过以35000xg离心30分钟收集蛋白质团聚体并且保留溶解细胞级分的一个样品。团聚的蛋白质溶解于6M盐酸胍。使用在相应的GBS菌株细菌攻击中存活的注射了甲醛杀死的GBS菌株C388/90(Ia/c)细胞的小鼠血清通过蛋白质印迹分析表明溶解的和不溶的级分中都存在融合蛋白。

根据固定在His.Bind金属螯合树脂(Novagen，Madison，WI)上的与二价阳离子(Ni²⁺)结合的His.Tag序列(6个连续的组氨酸残基)的性质通过亲和层析进行从IPTG-诱导的AD494(DE3)/rpET的溶解级分纯化融合蛋白。使用的纯化方法是pET system Manual，第六版(Novagen，Madison，WI)中描述的那些。简要地说，将自IPTG诱导的100毫升培养物获得的成粒的细胞悬浮于4毫升结合缓冲液(5mM咪唑-500mMNaCl-20mM Tris-HClpH7.9)，超声，以39000xg离心20分钟去除残渣。过滤上清液(0.45μm孔径的膜)并且沉积在结合缓冲液中平衡的His.Bind树脂柱上。然后用10柱体积的结合缓冲液接着用6柱体积的洗涤缓冲液(20mM咪唑-500mMNaCl-20mM Tris-HClpH7.9)冲洗柱子。用洗脱缓冲液(1M咪唑-500mMNaCl-20mM Tris-HClpH7.9)洗脱硫氧还蛋白-His.Tag-GBS融合蛋白。通过在4℃下用3×1升PBS透析，从样品中去除盐和咪唑。

通过十二烷基硫酸钠(SDS)-聚丙烯酰胺树脂的考马斯染色，用这些蛋白质的系列稀释物和牛血清白蛋白标准(Pierce ChemicalCo.Rockford，Ill)估计从大肠杆菌溶解或不溶细胞质级分获得的融合蛋白的量。

实施例5λP_L启动子控制下GBS蛋白质的重组制备

GBS蛋白质的DNA编码区经启动子λP_L下游插入到翻译载体pURV22中。该质粒自p629(George等，1987，Bio/Technology5：600)衍生，从p629去除I型单纯疱疹病毒(HSV-I)糖蛋白(gD-1)的一部分的编码区，从质粒载体pUC4K(Pharmacia Biotech Canada Inc.，Baie D’Urfe，加拿大)获得的卡那霉素盒置换氨苄青霉素抗性基因。该载体包含λ噬菌体cI857温度敏感阻抑蛋白基因盒，其中缺失了功能PR启动子。温度从30-37℃提高至37-42℃范围cI857阻抑蛋白的灭活导致λP_L控制下的基因诱导。下游是BglII限制位点(AGATCT)和ATG：ACTAAGGAGGTTAGATCTATG的核糖体结合位点cro控制该基因的翻译。

根据供应商说明(Pharmacia Biotech Canada Inc.，Baie D’Urfe，加拿大；和New England Biolabs Ltd.，Mississauga，加拿大)使用限制酶和T4 DNA连接酶。根据Sambrook等所述(分子克隆：实验室手册，1989，冷泉港实验室出版社，N.Y.)进行DNA片段的琼脂糖凝胶电泳。根据Jayarao等(J.Clin.Microbiol.，1991，29：2774)中描述的方法制备GBS细菌的染色体DNA。使用DNA Thermal CyclerGeneAmp PCR系统2400(Perkin Elmer，San Jose，CA)进行通过聚合酶链反应(PCR)的DNA扩增反应。使用购自Qiagen(Chatsworth，CA)的质粒试剂盒纯化用于DNA测序的质粒。使用购自Qiagen(Chatsworth，CA)的QiaexII凝胶提取试剂盒从琼脂糖凝胶纯化DNA片段。通过Hanahan(DNA Clone，Glover(编著)pp.109-135，1985)描述的方法进行质粒转化。使用寡核苷酸合成仪394型(Perkin-ElmerCorp.，Applied Biosystems Div，(ABI)，Foster City，CA)合成的合成寡核苷酸进行基因组DNA插入片段的测序。使用Taq DyeDeoxy Terminator Cycle Sequencing试剂盒(ABI，Foster City，CA)通过PCR进行测序反应，并且在自动DNA测序仪373A(ABI，FosterCity，CA)上进行DNA电泳。使用Sequencer 3.0程序(Gene CodesCorporation，Ann Arbor，MI)进行DNA序列的组装。应用Gene Works2.45版程序(Intelligenetics，Inc.，Mountain ViewCA)进行DNA序列分析和它们的预测的多肽的分析。

使用包含分别加入限制酶切位点BglII(AGATCT)和XbaI(TCTAGA)的碱基延伸的寡聚物通过PCR从GBS菌株C388/90(Ia/c)的基因组DNA扩增GBS基因的编码区。使用购自Qiagen(Chatsworth，CA)的QiaexII凝胶提取试剂盒用琼脂糖凝胶纯化PCR产物，用限制酶BglII和XbaI消化，在乙醇沉淀之前用苯酚：氯仿提取。用限制酶BglII和XbaI消化包含pURV22载体，用苯酚：氯仿提取，然后乙醇沉淀之。BglII-XbaI基因组DNA片段连接BglII-XbaI pURV22载体，其中GBS基因在λPL启动子控制下。根据上文Hanahan的方法，将连接产物转化到大肠杆菌菌株XLI Blue MRF’(Δ(mcrA)183Δ(mcrCB-hsdSMR-mrr)173 endA1 supE44 thi-1 recA1 gyrA96 relA1 lac(F’proABlacI^qZΔM15Tn10(Tet^r))^c)(Stratagene，La Jolla，CA)中。通过将溶解的细胞在琼脂糖凝胶上进行电泳(Sambrook等，上文)分析来鉴定携带插入片段的带有转化体的质粒。使用Qiagen试剂盒(Qiagen，Chatsworth，CA)纯化重组pURV22质粒，并且通过DNA测序证实所述DNA插入片段的核苷酸序列。

250rpm搅拌下在34℃下，在每毫升含有50μg卡那霉素的LB肉汤中培养转化体XLI Blue MRF’/rpURV22，直到A₆₀₀达到0.6的值。为了诱导融合蛋白的产生，将细菌细胞在39℃再培养4小时，再悬浮于样品缓冲液中，沸腾10分钟并且在-20℃下保存。

实施例6CMV质粒pCMV-GH中亚克隆GBS蛋白基因

GBS蛋白DNA编码区插入到人生长激素(hGH)基因下游，其处于质粒载体pCMV-GH中的巨细胞病毒(CMV)启动子的转录控制下(Tang等，Nature，1992，356：152)。CMV启动子在大肠杆菌细胞中是没有功能的，但是施用真核细胞中的质粒时是活性的。所述载体也插入氨苄青霉素抗性基因。

使用包含加入限制酶切位点BglII(AGATCT)和HindIII(AAGCTT)的碱基延伸的寡聚物通过PCR从GBS菌株C388/90(Ia/c)的基因组DNA扩增所述基因的编码区。使用购自Qiagen(Chatsworth，CA)的QiaexII凝胶提取试剂盒用琼脂糖凝胶纯化PCR产物，用限制酶BglII和HindIII消化，在乙醇沉淀之前用苯酚：氯仿提取。用限制酶BglII和HindIII消化包含人生长激素的pCMV-GH载体(StephenA.Johnston博士的实验室，德克萨斯大学，生物化学系，Dallas，德克萨斯州)，用苯酚：氯仿提取，然后乙醇沉淀之。1.3-kb BglII-HindIII基因组DNA片段连接BamHI-HindIII pCMV-GH载体，产生CMV启动子控制下的hGH-GBS融合蛋白。根据上文Hanahan的方法该连接产物转化到大肠杆菌菌株DH5α(φ80 lacZ ΔM15 endA1 recA1 hsdR17(^rK^-mK⁺)supE44 thi-1λ^-gyrA1Δ(lacZYA-argF)U169)(GibcoBRL，Gaithersbury，MD)中。通过将溶解的细胞在琼脂糖凝胶上进行电泳(Sambrook等，上文)分析来鉴定携带插入片段的带有转化体的质粒。使用Qiagen试剂盒(Qiagen，Chatsworth，CA)纯化重组pCMV质粒，并且通过DNA测序证实所述DNA插入片段的核苷酸序列。

实施例7GBS蛋白质对GBS攻击的免疫活性

以三星期间隔用0.1毫升下面的抗原制剂对6-8周龄的四组12只雌性CD-1小鼠(Charles River，St-Constant，Quebec，加拿大)皮下注射三次：甲醛杀死的GBS菌株C388/90(6×10⁷cfu)，20μg来自不溶物(包函体)的硫氧还蛋白-His.Tag-GBS融合蛋白或者亲和纯化的(镍柱)来自大肠杆菌细胞质溶解级分的20μg融合蛋白，或者20μg亲和纯化的(镍柱)硫氧还蛋白-His.Tag对照多肽。向每一抗原制剂中加入20μgQuilA^TM(Cedarlane Laboratories Ltd.Hornby，加拿大)作为佐剂。在免疫之前(PB)和在免疫过程中第20天(TB1)，41天(TB2)和54天(TB3)从每一只小鼠获得血清样品。血清在-20℃下冷冻。

每一次注射融合蛋白之后记录ELISA效价的增加，表明好的初次应答和第二次和第三次施用后特异性体液免疫应答的加强。在免疫期最后，用从包函体获得的20μg融合蛋白免疫的组相应的ELISA效价的平均值是456145，相比之下，用得自大肠杆菌中可溶级分的蛋白质免疫的小鼠组是290133。后一结果提示从包函体获得的蛋白质比可溶蛋白质更具免疫原性。使用亲和纯化的硫氧还蛋白-His.Tag包被的平板在ELISA中的小鼠血清分析表明对于融合蛋白的硫氧还蛋白-His.Tag部分可忽略抗体效价。通过ELISA也试验了注射了重组融合蛋白的小鼠的血清对甲醛杀死的GBS菌株C388/90全细胞的反应性。重组融合蛋白免疫诱导的抗体也识别GBS细胞上它们的特异性表位，表明它们的构象足以接近天然的链球菌蛋白质来诱导交叉反应抗体。

为了证实免疫诱导的免疫应答能否保护抗GBS感染，用3.5×10⁵cfuGBS菌株C388/90(Ia/c)和1.2×10⁵cfu菌株NCS246(II/R)攻击小鼠，其结果分别在表3和4中说明。用对照硫氧还蛋白-His.Tag肽免疫的小鼠都不能保护不受两种GBS菌株的攻击，而用甲醛杀死的GBS菌株C388/90全细胞免疫的那些小鼠只提供抗同种攻击的保护。本发明硫氧还蛋白-His.Tag-GBS融合蛋白保护小鼠不受两种GBS菌株的感染。这些小鼠的血和脾培养物表明不存在任何GBS。

表3在GBS菌株C388/90(Ia/c)攻击下存活试验¹

免疫试剂	攻击下存活的小鼠数目	存活百分率(％)
免疫试剂	攻击下存活的小鼠数目	存活百分率(％)	硫氧还蛋白-His.Tag²	1/6	17
甲醛杀死的C388/90细胞³	6/6	100	硫氧还蛋白-His.Tag²	1/6	17
甲醛杀死的C388/90细胞³	6/6	100	硫氧还蛋白-His.Tag-GBS融合蛋白(包函体制剂)⁴	6/6	100
硫氧还蛋白-His.Tag-GBS融合蛋白(细胞质级分)⁴	6/6	100	硫氧还蛋白-His.Tag-GBS融合蛋白(包函体制剂)⁴	6/6	100

¹腹膜内施用调节到3.5×10⁵cfu的1毫升Todd-Hewitt培养基；

²施用20μg；存活小鼠后腿麻痹；对血液和脾检测GBS；

³施用6×10⁷cfu；

⁴施用20μg。

表4在GBS菌株NCS246(II/R)攻击下存活试验¹

免疫试剂	攻击下存活的小鼠数目	存活百分率(％)
免疫试剂	攻击下存活的小鼠数目	存活百分率(％)	硫氧还蛋白-His.Tag²	0/6	0
甲醛杀死的C388/90细胞³	2/6	34	硫氧还蛋白-His.Tag²	0/6	0
甲醛杀死的C388/90细胞³	2/6	34	硫氧还蛋白-His.Tag-GBS融合蛋白(包函体制剂)²	5/5⁴	100
硫氧还蛋白-His.Tag-GBS融合蛋白(细胞质级分)²	6/6	100	硫氧还蛋白-His.Tag-GBS融合蛋白(包函体制剂)²	5/5⁴	100

¹腹膜内施用调节到1.2×10⁵cfu的1毫升含有GBS NC246(II/R)悬浮液的Todd-Hewitt培养基；

²施用20μg；

³施用6×10⁷cfu；

⁴一只小鼠在免疫期间死亡。

实施例8用重组GBS蛋白质免疫赋与抗试验性GBS感染的保护性

该实施例详细说明了通过用相应于SEQ ID NO：39的重组蛋白免疫保护小鼠抗致命GBS感染的保护作用。

以三星期间隔，使用从携带包含相应于SEQ ID NO：42的GBS基因的重组pURV22质粒载体的大肠杆菌菌株BLR(Novagen)纯化的20μg重组蛋白，在20μg QuilA^TM佐剂(Cedarlane Laboratories Ltd，Hornby，加拿大)存在下，对每组10只雌性CD-1小鼠(Charles River)皮下注射免疫三次，或者，作为对照，只使用PBS中的QuilA^TM注射。每一次免疫之前第1，22和43天和第三次注射之后第14天(57天)从眶下窦(orbital sinus)取血样。一星期之后，用大约10⁴至10⁶CFU的各种强毒株GBS攻击小鼠。在TSA/5％山羊血琼脂平板上平板培养GBS攻击种菌样品以确定CFU和核实攻击剂量。记录14天的死亡情况，并且在攻击后第14天，杀死存活的小鼠，并对血液和脾测定GBS微生物的存在。存活数据在表5中给出。

通过标准免疫测定法，对攻击前血清分析与GBS反应的抗体的存在。酶联免疫吸附测定和免疫印迹分析表明用大肠杆菌中产生的重组GBS蛋白免疫诱发了与重组和天然GBS蛋白质两者都反应的抗体。实施例9描述了对GBS应答的抗体。

表5相应于SEQ ID NO：39的重组GBS蛋白激发抗8种各异的GBS攻击菌株的保护作用的能力

	攻击菌株
	攻击菌株			免疫原	编号	类型	存活数目∶死亡数目¹
rGBS蛋白质没有	C388/90	Ia/c	8∶2(P＜0.0001)0∶10	免疫原	编号	类型	存活数目∶死亡数目¹
rGBS蛋白质没有	C388/90	Ia/c	8∶2(P＜0.0001)0∶10	rGBS蛋白质没有	NCS246	II/R	10∶0(P＝0.0012)3∶7
rGBS蛋白质没有	ATCC12401	Ib	10∶0(P＝0.001)3∶7	rGBS蛋白质没有	NCS246	II/R	10∶0(P＝0.0012)3∶7
rGBS蛋白质没有	ATCC12401	Ib	10∶0(P＝0.001)3∶7	rGBS蛋白质没有	NCS535	V	10∶0(P＝0.01)5∶5
rGBS蛋白质没有	NC9842	VI	10∶0(P＜0.0001)0∶10	rGBS蛋白质没有	NCS535	V	10∶0(P＝0.01)5∶5
rGBS蛋白质没有	NC9842	VI	10∶0(P＜0.0001)0∶10	rGBS蛋白质NCS 915-F³没有	NCS915	III	7∶3(P＝0.0007)²1∶94∶6
rGBS蛋白质NCS 954-F没有	NCS954	III/R	7∶3(P＝0.002)4∶61∶9	rGBS蛋白质NCS 915-F³没有	NCS915	III	7∶3(P＝0.0007)²1∶94∶6
rGBS蛋白质NCS 954-F没有	NCS954	III/R	7∶3(P＝0.002)4∶61∶9	rGBS蛋白质COH1-F没有	COH1	III	4∶6(P＝0.0004)3∶70∶10

¹使用每组10只小鼠的组，给出了感染存活的小鼠数目和死亡的小鼠的数目。应用对于非参数分析的logrank测定，将相应于重组GBS蛋白免疫的动物的成活率曲线与相应于模拟免疫的动物的成活率曲线相比较。

²对NCS915-F-免疫的动物的比较分析。

³在QuilA^TM佐剂存在下用甲醛杀死的GBS免疫动物。

在攻击后第14天，来自存活小鼠的所有血培养是阴性的。来自存活小鼠的所有脾培养是阴性的，除了实验MB-11的几只小鼠。

实施例9用重组GBS蛋白质接种激发对GBS的免疫应答

根据实施例8所述，用相应于SEQ ID NO：39的重组GBS蛋白质对10只雌性CD-1小鼠皮下免疫。为了评价对天然GBS蛋白的抗体反应，通过ELISA，使用选自III型NCS954菌株，Ib菌株ATCC12401，V型菌株NCS535或VI型菌株NCS9842的甲醛杀死的GBS细胞包被的平板，对在每一次免疫之前和在第三次免疫之后14天收集的血样血清测试抗体与GBS细胞的反应性。对GBS细胞提取物和纯化的重组抗原的蛋白质印迹测定证实产生的抗体对GBS蛋白质的特异性。图10中显示的结果清楚地证明动物对用作免疫原的重组GBS蛋白质强烈应答，相应的抗体效价中间值根据包被的抗原对于第三次免疫之后收集的血清来说在12000和128000之间变化。当在1∶100稀释度下测定时，所有免疫前血清是负值。在一次注射重组GBS蛋白之后每一只动物的血清中可检测到与GBS反应的抗体。

实施例10本发明GBS蛋白的抗原保守性

使用特异于本发明的GBS蛋白的单克隆抗体(MAbs)来证明所有的GBS产生该表面抗原，并且其抗原性高度保守。

收集68个GBS分离物来评价GBS-特异性MAbs的反应性。从加拿大Northern Alberta省立公共健康实验室，链球菌国家中心；魁北克大学中心医院，Pavillon CHUL，魁北克，加拿大；美国典型培养物保藏中心，USA；加拿大魁北克Laboratoire de Sante Publique，美国西雅图儿童医院和医药中心获得这些菌株。对下面菌株平行测试所有8个单克隆抗体：血清型Ia或Ia/c的6个分离物，血清型Ib的3个分离物，血清型II的4个分离物，血清型IV的2个分离物，血清型V的2个分离物，血清型VI的2个分离物，血清型VII的2个分离物，血清型VIII的1个分离物，没有表征血清型的10个分离物和3个牛无菌链球菌菌株。Mab 3A2也与另外的GBS反应：血清型Ia/c的9个分离物和血清型V的10个分离物。37℃下5％CO₂气氛下在血琼脂板上将菌株培养过夜。在-70℃下在含有20％(v/v)甘油的心浸液肉汤中保藏培养物。

为了获得GBS蛋白质特异性MAbs，以三星期间隔，用在20％QuilA^TM佐剂存在下的20μg纯化的重组GBS蛋白质(SEQ ID NO：44)三次免疫小鼠。从免疫小鼠回收的脾细胞与先前描述的非分泌SP2/0骨髓瘤细胞系(Hamel，J.等，1987，J.Med.Microbiol.23：163-170)融合产生杂交瘤细胞系。根据先前所述(Hamel，J.等，1987，J.Med.Microbiol.23：163-170)，使用甲醛灭活的GBS和纯化的重组GBS蛋白质(SEQ ID NO：39或44)作为包被抗原，通过ELISA对杂交克隆上清液测试特异抗体产生。通过限制稀释度克隆特异的杂化物，扩展，并且在液氮中冷冻。实施例4和5中存在重组GBS蛋白质的产生。通过使用不连续的Laemmli的缓冲体系根据生产商说明通过电泳解离纯化的重组GBS蛋白质或甲醛灭活的GBS，然后转移到硝基纤维素膜上用于蛋白质免疫印迹测定，如先前所述(Martin等，1992，Infect.Immun.60：2718-2725)。

蛋白质免疫印迹实验清楚地表明所有8个单克隆抗体识别相应于纯化的重组GBS蛋白质(SEQ ID NO：39)的蛋白质带。这些单克隆抗体还与迄今为止试验的每一种GBS分离物中存在的蛋白质带反应。表6中给出了这些GBS特异性单克隆抗体的反应性。每一种单克隆抗体与所有46种GBS很好地反应。另外，这些单克隆抗体也识别测试过的牛源的3个无菌链球菌菌株。MAb3A2还识别19种GBS；血清型Ia/c的9个分离物和血清型V的10个分离物。对其它MAbs没有测定抗这些另外的菌株的性能。

这些结果证明迄今为止测定的所有65种GBS和牛源的3个无菌链球菌菌株都产生GBS蛋白质(SEQ ID NO：39)。更重要的是，这些结果清楚地证明这8个GBS-特异性MAbs识别的表位分布广泛并且在GBS中是保守的。这些结果还表明这些表位不限制于血清学相关的分离物，因为测试了所有已知GBS血清型，包括主要疾病引发组的代表。

结论是，该实施例中存在的数据清楚地证明所有的GBS都产生本发明的GBS蛋白质并且其抗原性高度保守。

表6.根据蛋白质印迹评价的8个GBS蛋白质特异性单克隆抗体与不同的无菌链球菌菌株的反应性。

图	MAbs识别的无菌链球菌菌株各血清型的数目。
图	MAbs识别的无菌链球菌菌株各血清型的数目。													Ia或Ia/c(6)	Ib(3)	II(4)	III(4)	IV(2)	V(2)	VI(2)	VII(2)	VIII(1)	NT(10)²	总计(26)	牛(3)
3A2¹	6	3	4	4	2	2	2	2	1	10	46	3		Ia或Ia/c(6)	Ib(3)	II(4)	III(4)	IV(2)	V(2)	VI(2)	VII(2)	VIII(1)	NT(10)²	总计(26)	牛(3)
3A2¹	6	3	4	4	2	2	2	2	1	10	46	3	5A12	6	3	4	4	2	2	2	2	1	10	46	3
6G11	6	3	4	4	2	2	2	2	1	10	46	2	5A12	6	3	4	4	2	2	2	2	1	10	46	3
6G11	6	3	4	4	2	2	2	2	1	10	46	2	8B9	6	3	4	4	2	2	2	2	1	10	46	3
8E11	6	3	4	4	2	2	2	2	1	10	46	3	8B9	6	3	4	4	2	2	2	2	1	10	46	3
8E11	6	3	4	4	2	2	2	2	1	10	46	3	12B12	6	3	4	4	2	2	2	2	1	10	46	3
18F11	6	3	4	4	2	2	2	2	1	10	46	3	12B12	6	3	4	4	2	2	2	2	1	10	46	3
18F11	6	3	4	4	2	2	2	2	1	10	46	3	20G2	6	3	4	4	2	2	2	2	1	10	46	3

¹MAb3A2识别血清型Ia/c的9个另外的菌株和血清型V的10个菌株。

²这些菌株没有表征血清型。

序列表

<110>BioChem Vaccins

RIOUX，Clément

DENIS，Martin

BRODEUR，Bernard R.

HAMEL，Josée

CHARLEBOIS，Isabelle

BOYER，Martine

<120>新的B组链球菌抗原

<130>12806-9PCT

<150>60/075,425

<151>1998-02-20

<160>44

<170>FastSEQ for Windows Version 3.0

<210>1

<211>4514

<212>DNA

<213>链球菌

<220>

<221>CDS

<222>(3)...(464)

<221>CDS

<222>(534)...(887)

<223>

<221>CDS

<222>(1024)...(1767)

<221>CDS

<222>(1841)...(4288)

<221>CDS

<222>(2735)...(4288)

<400>1

ta tct ggc aaa gag cca gct aat cgt ttt agt tgg gct aaa aat aaa 47

Ser Gly Lys Glu Pro Ala Asn Arg Phe Ser Trp Ala Lys Asn Lys

1 5 10 15

tta tta atc aat gga ttc att gca act cta gca gca act atc tta ttt 95

Leu Leu Ile Asn Gly Phe Ile Ala Thr Leu Ala Ala Thr Ile Leu Phe

20 25 30

ttt gca gtt caa ttc ata ggt ctt aaa cca gat tac cct gga aaa acc 143

Phe Ala Val Gln Phe Ile Gly Leu Lys Pro Asp Tyr Pro Gly Lys Thr

35 40 45

tac ttt att atc cta ttg aca gca tgg act ttg atg gca tta gta act 191

Tyr Phe Ile Ile Leu Leu Thr Ala Trp Thr Leu Met Ala Leu Val Thr

50 55 60

gct tta gtg gga tgg gat aat agg tat ggt tcc ttc ttg tcg tta tta 239

Ala Leu Val Gly Trp Asp Asn Arg Tyr Gly Ser Phe Leu Ser Leu Leu

65 70 75

ata tta tta ttc cag ctt ggt tca agc gca gga act tac cca ata gaa 287

Ile Leu Leu Phe Gln Leu Gly Ser Ser Ala Gly Thr Tyr Pro Ile Glu

80 85 90 95

ttg agt cct aag ttc ttt caa aca att caa cca ttt tta ccg atg act 335

Leu Ser Pro Lys Phe Phe Gln Thr Ile Gln Pro Phe Leu Pro Met Thr

100 105 110

tac tct gtt tca gga tta aga gag acc atc tcg ttg acg gga gac gtt 383

Tyr Ser Val Ser Gly Leu Arg Glu Thr Ile Ser Leu Thr Gly Asp Val

115 120 125

aac cat caa tgg aga atg cta gta atc ttt tta gta tca tcg atg ata 431

Asn His Gln Trp Arg Met Leu Val Ile Phe Leu Val Ser Ser Met Ile

130 135 140

ctt gct ctt ctt att tat cgt aaa caa gaa gat taatagaaag tatctagtga 484

Leu Ala Leu Leu Ile Tyr Arg Lys Gln Glu Asp

145 150

tagactaaca gtatgatatg gtatgtcaaa gtatttagga ggagaagat atg tct act 542

Met Ser Thr

155

tta aca ata att att gca aca tta act gct ttg gaa cat ttt tat att 590

Leu Thr Ile Ile Ile Ala Thr Leu Thr Ala Leu Glu His Phe Tyr Ile

160 165 170

atg tat ttg gag acg tta gcc acc cag tca aat atg act ggg aag att 638

Met Tyr Leu Glu Thr Leu Ala Thr Gln Ser Asn Met Thr Gly Lys Ile

175 180 185

ttt agt atg tct aaa gaa gag ttg tca tat tta ccc gtt att aaa ctt 686

Phe Ser Met Ser Lys Glu Glu Leu Ser Tyr Leu Pro Val Ile Lys Leu

190 195 200 205

ttt aag aat caa ggt gta tac aac ggc ttg att ggc cta ttc ctc ctt 734

Phe Lys Asn Gln Gly Val Tyr Asn Gly Leu Ile Gly Leu Phe Leu Leu

210 215 220

tat ggg tta tat att tca cag aat caa gaa att gta gct gtt ttt tta 782

Tyr Gly Leu Tyr Ile Ser Gln Asn Gln Glu Ile Val Ala Val Phe Leu

225 230 235

atc aat gta ttg cta gtt gct att tat ggt gct ttg aca gtt gat aaa 830

Ile Asn Val Leu Leu Val Ala Ile Tyr Gly Ala Leu Thr Val Asp Lys

240 245 250

aaa atc tta tta aaa cag ggt ggt tta cct ata tta gct ctt tta aca 878

Lys Ile Leu Leu Lys Gln Gly Gly Leu Pro Ile Leu Ala Leu Leu Thr

255 260 265

ttc tta ttt taatactact tagccgttcg atttagttga acggctttta 927

Phe Leu Phe

270

gtaatcattt ttttctcata atacaggtag tttaagtaat ttgtctttaa aaatagtata 987

atataactac gaattcaaag agaggtgact ttgatt atg act gag aac tgg tta 1041

Met Thr Glu Asn Trp Leu

275

cat act aaa gat ggt tca gat att tat tat cgt gtc gtt ggt caa ggt 1089

His Thr Lys Asp Gly Ser Asp Ile Tyr Tyr Arg Val Val Gly Gln Gly

280 285 290

caa ccg att gtt ttt tta cat ggc aat agc tta agt agt cgc tat ttt 1137

Gln Pro Ile Val Phe Leu His Gly Asn Ser Leu Ser Ser Arg Tyr Phe

295 300 305 310

gat aag caa ata gca tat ttt tct aag tat tac caa gtt att gtt atg 1185

Asp Lys Gln Ile Ala Tyr Phe Ser Lys Tyr Tyr Gln Val Ile Val Met

315 320 325

gat agt aga ggg cat ggc aaa agt cat gca aag cta aat acc att agt 1233

Asp Ser Arg Gly His Gly Lys Ser His Ala Lys Leu Asn Thr Ile Ser

330 335 340

ttc agg caa ata gca gtt gac tta aag gat atc tta gtt cat tta gag 1281

Phe Arg Gln Ile Ala Val Asp Leu Lys Asp Ile Leu Val His Leu Glu

345 350 355

att gat aaa gtt ata ttg gta ggc cat agc gat ggt gcc aat tta gct 1329

Ile Asp Lys Val Ile Leu Val Gly His Ser Asp Gly Ala Asn Leu Ala

360 365 370

tta gtt ttt caa acg atg ttt cca ggt atg gtt aga ggg ctt ttg ctt 1377

Leu Val Phe Gln Thr Met Phe Pro Gly Met Val Arg Gly Leu Leu Leu

375 380 385 390

aat tca ggg aac ctg act att cat ggt cag cga tgg tgg gat att ctt 1425

Asn Ser Gly Asn Leu Thr Ile His Gly Gln Arg Trp Trp Asp Ile Leu

395 400 405

tta gta agg att gcc tat aaa ttc ctt cac tat tta ggg aaa ctc ttt 1473

Leu Val Arg Ile Ala Tyr Lys Phe Leu His Tyr Leu Gly Lys Leu Phe

410 415 420

ccg tat atg agg caa aaa gct caa gtt att tcg ctt atg ttg gag gat 1521

Pro Tyr Met Arg Gln Lys Ala Gln Val Ile Ser Leu Met Leu Glu Asp

425 430 435

ttg aag att agt cca gct gat tta cag cat gtg tca act cct gta atg 1569

Leu Lys Ile Ser Pro Ala Asp Leu Gln His Val Ser Thr Pro Val Met

440 445 450

gtt ttg gtt gga aat aag gac ata att aag tta aat cat tct aag aaa 1617

Val Leu Val Gly Asn Lys Asp Ile Ile Lys Leu Asn His Ser Lys Lys

455 460 465 470

ctt gct tct tat ttt cca agg ggg gag ttt tat tct tta gtt ggc ttt 1665

Leu Ala Ser Tyr Phe Pro Arg Gly Glu Phe Tyr Ser Leu Val Gly Phe

475 480 485

ggg cat cac att att aag caa gat tcc cat gtt ttt aat att att gca 1713

Gly His His Ile Ile Lys Gln Asp Ser His Val Phe Asn Ile Ile Ala

490 495 500

aaa aag ttt atc aac gat acg ttg aaa gga gaa att gtt gaa aaa gct 1761

Lys Lys Phe Ile Asn Asp Thr Leu Lys Gly Glu Ile Val Glu Lys Ala

505 510 515

aat tga aaaagtcaaa tcactgactt ctgtgattaa aattgtattt tttatatctg 1817

Asn7*

ttttagtgct tattattgtt gaa atg att cat ttg aaa cga act att tct gtt 1870

Met Ile His Leu Lys Arg Thr Ile Ser Val

520 525

gag caa cta aag agt gtt ttt ggg caa tta tct cca atg aat ctt ttc 1918

Glu Gln Leu Lys Ser Val Phe Gly Gln Leu Ser Pro Met Asn Leu Phe

530 535 540 545

tta att atc ctt gtg ggg gtt atc gct gtc tta ccg aca acc gga tat 1966

Leu Ile Ile Leu Val Gly Val Ile Ala Val Leu Pro Thr Thr Gly Tyr

550 555 560

gac ttt gta ctg aat gga ctt tta cgt aca gat aaa agc aaa agg tat 2014

Asp Phe Val Leu Asn Gly Leu Leu Arg Thr Asp Lys Ser Lys Arg Tyr

565 570 575

att tta cag act agt tgg tgt atc aac act ttt aat aac ttg tca gga 2062

Ile Leu Gln Thr Ser Trp Cys Ile Asn Thr Phe Asn Asn Leu Ser Gly

580 585 590

ttc ggt ggc tta atc gat att ggg ttg cgc atg gct ttt tat ggt aaa 2110

Phe Gly Gly Leu Ile Asp Ile Gly Leu Arg Met Ala Phe Tyr Gly Lys

595 600 605

aaa ggt caa gag aag agt gac cta aga gaa gtg act cgt ttt tta ccc 2158

Lys Gly Gln Glu Lys Ser Asp Leu Arg Glu Val Thr Arg Phe Leu Pro

610 615 620 625

tat ctt att tct ggt ctg tca ttt att agt gtg att gcc tta atc atg 2206

Tyr Leu Ile Ser Gly Leu Ser Phe Ile Ser Val Ile Ala Leu Ile Met

630 635 640

agc cat att ttt cat gcc aaa gct agt gtt gat tac tat tat ttg gta 2254

Ser His Ile Phe His Ala Lys Ala Ser Val Asp Tyr Tyr Tyr Leu Val

645 650 655

tta att ggt gct agt atg tat ttt cct gtt att tat tgg att tct ggt 2302

Leu Ile Gly Ala Ser Met Tyr Phe Pro Val Ile Tyr Trp Ile Ser Gly

660 665 670

cat aaa gga agc cat tat ttc gga gat atg cca tct agt act cgt ata 2350

His Lys Gly Ser His Tyr Phe Gly Asp Met Pro Ser Ser Thr Arg Ile

675 680 685

aaa tta ggt gtt gtt tct ttt ttt gaa tgg gga tgt gcg gcc gca gca 2398

Lys Leu Gly Val Val Ser Phe Phe Glu Trp Gly Cys Ala Ala Ala Ala

690 695 700 705

ttt ata att atc ggt tat tta atg ggc att cat cta cca gtt tat aaa 2446

Phe Ile Ile Ile Gly Tyr Leu Met Gly Ile His Leu Pro Val Tyr Lys

710 715 720

att tta cca cta ttt tgt att ggt tgt gcc gtc ggg att gta tcc ctt 2494

Ile Leu Pro Leu Phe Cys Ile Gly Cys Ala Val Gly Ile Val Ser Leu

725 730 735

att ccc ggt gga tta gga agt ttt gaa tta gtt cta ttt aca ggg ttt 2542

Ile Pro Gly Gly Leu Gly Ser Phe Glu Leu Val Leu Phe Thr Gly Phe

740 745 750

gct gcc gag gga cta cct aaa gaa act gtg gtt gca tgg tta tta ctt 2590

Ala Ala Glu Gly Leu Pro Lys Glu Thr Val Val Ala Trp Leu Leu Leu

755 760 765

tat cgt tta gcc tac tat att att cca ttc ttt gca ggt atc tat ttc 2638

Tyr Arg Leu Ala Tyr Tyr Ile Ile Pro Phe Phe Ala Gly Ile Tyr Phe

770 775 780 785

ttt atc cat tat tta ggt agt caa ata aat caa cgt tat gaa aat gtc 2686

Phe Ile His Tyr Leu Gly Ser Gln Ile Asn Gln Arg Tyr Glu Asn Val

790 795 800

ccg aaa gag tta gta tca act gtt cta caa acc atg gtg agc cat ttg 2734

Pro Lys Glu Leu Val Ser Thr Val Leu Gln Thr Met Val Ser His Leu

805 810 815

atg cgt att tta ggt gca ttc tta ata ttt tca aca gca ttt ttt gaa 2782

Met Arg Ile Leu Gly Ala Phe Leu Ile Phe Ser Thr Ala Phe Phe Glu

820 825 830

aat att act tat att atg tgg ttg cag aag cta ggc ttg gac cca tta 2830

Asn Ile Thr Tyr Ile Met Trp Leu Gln Lys Leu Gly Leu Asp Pro Leu

835 840 845

caa gaa caa atg tta tgg cag ttt cca ggt tta ttg ctg ggg gtt tgt 2878

Gln Glu Gln Met Leu Trp Gln Phe Pro Gly Leu Leu Leu Gly Val Cys

850 855 860 865

ttt att ctc tta gct aga act att gat caa aaa gtg aaa aat gct ttt 2926

Phe Ile Leu Leu Ala Arg Thr Ile Asp Gln Lys Val Lys Asn Ala Phe

870 875 880

cca att gct att atc tgg att act ttg aca ttg ttt tat ctt aat tta 2974

Pro Ile Ala Ile Ile Trp Ile Thr Leu Thr Leu Phe Tyr Leu Asn Leu

885 890 895

ggt cat att agt tgg cga cta tct ttc tgg ttt att tta cta ttg tta 3022

Gly His Ile Ser Trp Arg Leu Ser Phe Trp Phe Ile Leu Leu Leu Leu

900 905 910

ggc tta tta gtc att aag cca act ctc tat aaa aaa caa ttt att tat 3070

Gly Leu Leu Val Ile Lys Pro Thr Leu Tyr Lys Lys Gln Phe Ile Tyr

915 920 925

agc tgg gaa gag cgt att aag gat gga atc att atc gtt agt tta atg 3118

Ser Trp Glu Glu Arg Ile Lys Asp Gly Ile Ile Ile Val Ser Leu Met

930 935 940 945

gga gtt cta ttt tat att gca gga cta cta ttc cct atc agg gct cat 3166

Gly Val Leu Phe Tyr Ile Ala Gly Leu Leu Phe Pro Ile Arg Ala His

950 955 960

att aca ggt ggt agt att gaa cgc ctg cat tat atc ata gca tgg gag 3214

Ile Thr Gly Gly Ser Ile Glu Arg Leu His Tyr Ile Ile Ala Trp Glu

965 970 975

ccg ata gca ttg gct acg ttg att ctt act ctc gtt tat tta tgt ttg 3262

Pro Ile Ala Leu Ala Thr Leu Ile Leu Thr Leu Val Tyr Leu Cys Leu

980 985 990

gtt aag att tta caa gga aaa tct tgt cag att ggt gat gtg ttc aat 3310

Val Lys Ile Leu Gln Gly Lys Ser Cys Gln Ile Gly Asp Val Phe Asn

995 1000 1005

gtg gat cgt tat aaa aaa cta ctt caa gct tac ggt ggt tct tcg gat 3358

Val Asp Arg Tyr Lys Lys Leu Leu Gln Ala Tyr Gly Gly Ser Ser Asp

1010 1015 1020 025

agc ggt tta gcc ttt tta aat gat aaa agg ctc tac tgg tac caa aaa 3406

Ser Gly Leu Ala Phe Leu Asn Asp Lys Arg Leu Tyr Trp Tyr Gln Lys

1030 1035 1040

aat gga gaa gat tgc gtt gcg ttc caa ttt gta att gtc aat aat aaa 3454

Asn Gly Glu Asp Cys Val Ala Phe Gln Phe Val Ile Val Asn Asn Lys

1045 1050 1055

tgt ctt att atg ggg gaa cca gcc ggt gat gac act tat att cgt gaa 3502

Cys Leu Ile Met Gly Glu Pro Ala Gly Asp Asp Thr Tyr Ile Arg Glu

1060 1065 1070

gct att gaa tcg ttt att gat gat gct gat aag cta gac tat gac ctt 3550

Ala Ile Glu Ser Phe Ile Asp Asp Ala Asp Lys Leu Asp Tyr Asp Leu

1075 1080 1085

gcc ttt tac agt att gga cag aag ttg aca cta ctt tta cat gag tat 3598

Val Phe Tyr Ser Ile Gly Gln Lys Leu Thr Leu Leu Leu His Glu Tyr

1090 1095 1100 1105

ggt ttt gac ttt atg aaa gtt ggt gag gat gct tta gtt aat tta gaa 3646

Gly Phe Asp Phe Met Lys Val Gly Glu Asp Ala Leu Val Asn Leu Glu

1110 1115 1120

acg ttt act ctt aaa ggg aat aag tac aaa cct ttc aga aat gcc cta 3694

Thr Phe Thr Leu Lys Gly Asn Lys Tyr Lys Pro Phe Arg Asn Ala Leu

1125 1130 1135

aat aga gtt gaa aag gat ggt ttc tat ttc gaa gtt gta caa tcg cca 3742

Asn Arg Val Glu Lys Asp Gly Phe Tyr Phe Glu Val Val Gln Ser Pro

1140 1145 1150

cat agc caa gag cta cta aat agt ttg gaa gag att tct aat act tgg 3790

His Ser Gln Glu Leu Leu Asn Ser Leu Glu Glu Ile Ser Asn Thr Trp

1155 1160 1165

tta gaa gga cgc cct gaa aaa ggt ttc tca cta gga tat ttt aat aaa 3838

Leu Glu Gly Arg Pro Glu Lys Gly Phe Ser Leu Gly Tyr Phe Agn Lyg

1170 1175 1180 1185

gat tat ttc caa caa gcc cca ata gct ttg gta aaa aat gct gaa cac 3886

Asp Tyr Phe Gln Gln Ala Pro Ile Ala Leu Val Lys Asn Ala Glu His

1190 1195 1200

gaa gtt gtt gct ttt gct aat att atg cca aac tat gaa aag agt att 3934

Glu Val Val Ala Phe Ala Asn Ile Met Pro Asn Tyr Glu Lys Ser Ile

1205 1210 1215

atc tct att gat tta atg cgt cac gat aaa cag aaa att ccg aat ggc 3982

Ile Ser Ile Asp Leu Met Arg His Asp Lys Gln Lys Ile Pro Asn Gly

1220 1225 1230

gtt atg gat ttc ctc ttt tta tca tta ttc tct tat tat caa gag aag 4030

Val Met Asp Phe Leu Phe Leu Ser Leu Phe Ser Tyr Tyr Gln Glu Lys

1235 1240 1245

gga tac cac tat ttt gat ttg ggg atg gca cct tta tca gga gtt ggt 4078

Gly Tyr His Tyr Phe Asp Leu Gly Met Ala Pro Leu Ser Gly Val Gly

1250 1255 1260 1265

cgc gtt gaa aca agt ttt gct aaa gag aga atg gcg tat ctt gtc tat 4126

Arg Val Glu Thr Ser Phe Ala Lys Glu Arg Met Ala Tyr Leu Val Tyr

1270 1275 1280

cat ttc ggt agt cat ttc tac tca ttt aat ggt tta cac aag tat aag 4174

His Phe Gly Ser His Phe Tyr Ser Phe Asn Gly Leu His Lys Tyr Lys

1285 1290 1295

aag aag ttt aca cca ttg tgg tcg gaa cgt tat att tct tgt tct cgt 4222

Lys Lys Phe Thr Pro Leu Trp Ser Glu Arg Tyr Ile Ser Cys Ser Arg

1300 1305 1310

tcg tcc tgg tta att tgt gct att tgt gcc cta tta atg gaa gat agt 4270

Ser Ser Trp Leu Ile Cys Ala Ile Cys Ala Leu Leu Met Glu Asp Ser

1315 1320 1325

aaa att aag att gtt aaataagctttat ttggcaatta aaaagagcat 4318

Lys Ile Lys Ile Val Lys

1330 1335

gtcatgcgac atgctctttt taaatcattt aataccattg attgcttgaa tctactttat 4378

aatatgatgt gcttttaaat attgtttagc tactgtagct gctgatttat gctttacagc 4438

tacttggtag ttcatttctt gcatttcttt ttcagtgata tgaccagcaa gtttattgag 4498

agcttttttt acttga 4514

<210>2

<211>154

<212>蛋白质

<213>链球菌

<400>2

Ser Gly Lys Glu Pro Ala Asn Arg Phe Ser Trp Ala Lys Asn Lys Leu

1 5 10 15

Leu Ile Asn Gly Phe Ile Ala Thr Leu Ala Ala Thr Ile Leu Phe Phe

20 25 30

Ala Val Gln Phe Ile Gly Leu Lys Pro Asp Tyr Pro Gly Lys Thr Tyr

35 40 45

Phe Ile Ile Leu Leu Thr Ala Trp Thr Leu Met Ala Leu Val Thr Ala

50 55 60

Leu Val Gly Trp Asp Asn Arg Tyr Gly Ser Phe Leu ser Leu Leu Ile

65 70 75 80

Leu Leu Phe Gln Leu Gly Ser Ser Ala Gly Thr Tyr Pro Ile Glu Leu

85 90 95

Ser Pro Lys Phe Phe Gln Thr Ile Gln Pro Phe Leu Pro Met Thr Tyr

100 105 110

Ser Val Ser Gly Leu Arg Glu Thr Ile Ser Leu Thr Gly Asp Val Asn

115 120 125

His Gln Trp Arg Met Leu Val Ile Phe Leu Val Ser Ser Met Ile Leu

130 135 140

Ala Leu Leu Ile Tyr Arg Lys Gln Glu Asp

145 150

<210>3

<211>118

<212>蛋白质

<213>链球菌

<400>3

Met Ser Thr Leu Thr Ile Ile Ile Ala Thr Leu Thr Ala Leu Glu His

1 5 10 15

Phe Tyr Ile Met Tyr Leu Glu Thr Leu Ala Thr Gln Ser Asn Met Thr

20 25 30

Gly Lys Ile Phe Ser Met Ser Lys Glu Glu Leu Ser Tyr Leu Pro Val

35 40 45

Ile Lys Leu Phe Lys Asn Gln Gly Val Tyr Asn Gly Leu Ile Gly Leu

50 55 60

Phe Leu Leu Tyr Gly Leu Tyr Ile Ser Gln Asn Gln Glu Ile Val Ala

65 70 75 80

Val Phe Leu Ile Asn Val Leu Leu Val Ala Ile Tyr Gly Ala Leu Thr

85 90 95

Val Asp Lys Lys Ile Leu Leu Lys Gln Gly Gly Leu Pro Ile Leu Ala

100 105 110

Leu Leu Thr Phe Leu Phe

115

<210>4

<211>247

<212>蛋白质

<213>链球菌

<400>4

Met Thr Glu Asn Trp Leu His Thr Lys Asp Gly Ser Asp Ile Tyr Tyr

1 5 10 15

Arg Val Val Gly Gln Gly Gln Pro Ile Val Phe Leu His Gly Asn Ser

20 25 30

Leu Ser Ser Arg Tyr Phe Asp Lys Gln Ile Ala Tyr Phe Ser Lys Tyr

35 40 45

Tyr Gln Val Ile Val Met Asp Ser Arg Gly His Gly Lys Ser His Ala

50 55 60

Lys Leu Asn Thr Ile Ser Phe Arg Gln Ile Ala Val Asp Leu Lys Asp

65 70 75 80

Ile Leu Val His Leu Glu Ile Asp Lys Val Ile Leu Val Gly His Ser

85 90 95

Asp Gly Ala Asn Leu Ala Leu Val Phe Gln Thr Met Phe Pro Gly Met

100 105 110

Val Arg Gly Leu Leu Leu Asn Ser Gly Asn Leu Thr Ile His Gly Gln

115 120 125

Arg Trp Trp Asp Ile Leu Leu Val Arg Ile Ala Tyr Lys Phe Leu His

130 135 140

Tyr Leu Gly Lys Leu Phe Pro Tyr Met Arg Gln Lys Ala Gln Val Ile

145 150 155 160

Ser Leu Met Leu Glu Asp Leu Lys Ile Ser Pro Ala Asp Leu Gln His

165 170 175

Val Ser Thr Pro Val Met Val Leu Val Gly Asn Lys Asp Ile Ile Lys

180 185 190

Leu Asn His Ser Lys Lys Leu Ala Ser Tyr Phe Pro Arg Gly Glu Phe

195 200 205

Tyr Ser Leu Val Gly Phe Gly His His Ile Ile Lys Gln Asp Ser His

210 215 220

Val Phe Asn Ile Ile Ala Lys Lys Phe Ile Asn Asp Thr Leu Lys Gly

225 230 235 240

Glu Ile Val Glu Lys Ala Asn

245

<210>5

<211>816

<212>蛋白质

<213>链球菌

<400>5

Met Ile His Leu Lys Arg Thr Ile Ser Val Glu Gln Leu Lys Ser Val

1 5 10 15

Phe Gly Gln Leu Ser Pro Met Asn Leu Phe Leu Ile Ile Leu Val Gly

20 25 30

Val Ile Ala Val Leu Pro Thr Thr Gly Tyr Asp Phe Val Leu Asn Gly

35 40 45

Leu Leu Arg Thr Asp Lys Ser Lys Arg Tyr Ile Leu Gln Thr Ser Trp

50 55 60

Cys Ile Asn Thr Phe Asn Asn Leu Ser Gly Phe Gly Gly Leu Ile Asp

65 70 75 80

Ile Gly Leu Arg Met Ala Phe Tyr Gly Lys Lys Gly Gln Glu Lys Ser

85 90 95

Asp Leu Arg Glu Val Thr Arg Phe Leu Pro Tyr Leu Ile Ser Gly Leu

100 105 110

Ser Phe Ile Ser Val Ile Ala Leu Ile Met Ser His Ile Phe His Ala

115 120 125

Lys Ala Ser Val Asp Tyr Tyr Tyr Leu Val Leu Ile Gly Ala Ser Met

130 135 140

Tyr Phe Pro Val Ile Tyr Trp Ile Ser Gly His Lys Gly Ser His Tyr

145 150 155 160

Phe Gly Asp Met Pro Ser Ser Thr Arg Ile Lys Leu Gly Val Val Ser

165 170 175

Phe Phe Glu Trp Gly Cys Ala Ala Ala Ala Phe Ile Ile Ile Gly Tyr

180 185 190

Leu Met Gly Ile His Leu Pro Val Tyr Lys Ile Leu Pro Leu Phe Cys

195 200 205

Ile Gly Cys Ala Val Gly Ile Val Ser Leu Ile Pro Gly Gly Leu Gly

210 215 220

Ser Phe Glu Leu Val Leu Phe Thr Gly Phe Ala Ala Glu Gly Leu Pro

225 230 235 240

Lys Glu Thr Val Val Ala Trp Leu Leu Leu Tyr Arg Leu Ala Tyr Tyr

245 250 255

Ile Ile Pro Phe Phe Ala Gly Ile Tyr Phe Phe Ile His Tyr Leu Gly

260 265 270

Ser Gln Ile Asn Gln Arg Tyr Glu Asn Val Pro Lys Glu Leu Val Ser

275 280 285

Thr Val Leu Gln Thr Met Val Ser His Leu Met Arg Ile Leu Gly Ala

290 295 300

Phe Leu Ile Phe Ser Thr Ala Phe Phe Glu Asn Ile Thr Tyr Ile Met

305 310 315 320

Trp Leu Gln Lys Leu Gly Leu Asp Pro Leu Gln Glu Gln Met Leu Trp

325 330 335

Gln Phe Pro Gly Leu Leu Leu Gly Val Cys Phe Ile Leu Leu Ala Arg

340 345 350

Thr Ile Asp Gln Lys Val Lys Asn Ala Phe Pro Ile Ala Ile Ile Trp

355 360 365

Ile Thr Leu Thr Leu Phe Tyr Leu Asn Leu Gly His Ile Ser Trp Arg

370 375 380

Leu Ser Phe Trp Phe Ile Leu Leu Leu Leu Gly Leu Leu Val Ile Lys

385 390 395 400

Pro Thr Leu Tyr Lys Lys Gln Phe Ile Tyr Ser Trp Glu Glu Arg Ile

405 410 415

Lys Asp Gly Ile Ile Ile Val Ser Leu Met Gly Val Leu Phe Tyr Ile

420 425 430

Ala Gly Leu Leu Phe Pro Ile Arg Ala His Ile Thr Gly Gly Ser Ile

435 440 445

Glu Arg Leu His Tyr Ile Ile Ala Trp Glu Pro Ile Ala Leu Ala Thr

450 455 460

Leu Ile Leu Thr Leu Val Tyr Leu Cys Leu Val Lys Ile Leu Gln Gly

465 470 475 480

Lys Ser Cys Gln Ile Gly Asp Val Phe Asn Val Asp Arg Tyr Lys Lys

485 490 495

Leu Leu Gln Ala Tyr Gly Gly Ser Ser Asp Ser Gly Leu Ala Phe Leu

500 505 510

Asn Asp Lys Arg Leu Tyr Trp Tyr Gln Lys Asn Gly Glu Asp Cys Val

515 520 525

Ala Phe Gln Phe Val Ile Val Asn Asn Lys Cys Leu Ile Met Gly Glu

530 535 540

Pro Ala Gly Asp Asp Thr Tyr Ile Arg Glu Ala Ile Glu Ser Phe Ile

545 550 555 560

Asp Asp Ala Asp Lys Leu Asp Tyr Asp Leu Val Phe Tyr Ser Ile Gly

565 570 575

Gln Lys Leu Thr Leu Leu Leu His Glu Tyr Gly Phe Asp Phe Met Lys

580 585 590

Val Gly Glu Asp Ala Leu Val Asn Leu Glu Thr Phe Thr Leu Lys Gly

595 600 605

Asn Lys Tyr Lys Pro Phe Arg Asn Ala Leu Asn Arg Val Glu Lys Asp

610 615 620

Gly Phe Tyr Phe Glu Val Val Gln Ser Pro His Ser Gln Glu Leu Leu

625 630 635 640

Asn Ser Leu Glu Glu Ile Ser Asn Thr Trp Leu Glu Gly Arg Pro Glu

645 650 655

Lys Gly Phe Ser Leu Gly Tyr Phe Asn Lys Asp Tyr Phe Gln Gln Ala

660 665 670

Pro Ile Ala Leu Val Lys Asn Ala Glu His Glu Val Val Ala Phe Ala

675 680 685

Asn Ile Met Pro Asn Tyr Glu Lys Ser Ile Ile Ser Ile Asp Leu Met

690 695 700

Arg His Asp Lys Gln Lys Ile Pro Asn Gly Val Met Asp Phe Leu Phe

705 710 715 720

Leu Ser Leu Phe Ser Tyr Tyr Gln Glu Lys Gly Tyr His Tyr Phe Asp

725 730 735

Leu Gly Met Ala Pro Leu Ser Gly Val Gly Arg Val Glu Thr Ser Phe

740 745 750

Ala Lys Glu Arg Met Ala Tyr Leu Val Tyr His Phe Gly Ser His Phe

755 760 765

Tyr Ser Phe Asn Gly Leu His Lys Tyr Lys Lys Lys Phe Thr Pro Leu

770 775 780

Trp Ser Glu Arg Tyr Ile Ser Cys Ser Arg Ser Ser Trp Leu Ile Cys

785 790 795 800

Ala Ile Cys Ala Leu Leu Met Glu Asp Ser Lys Ile Lys Ile Val Lys

805 810 815

<210>6

<211>518

<212>蛋白质

<213>链球菌

<400>6

Met Arg Ile Leu Gly Ala Phe Leu Ile Phe Ser Thr Ala Phe Phe Glu

1 5 10 15

Asn Ile Thr Tyr Ile Met Trp Leu Gln Lys Leu Gly Leu Asp Pro Leu

20 25 30

Gln Glu Gln Met Leu Trp Gln Phe Pro Gly Leu Leu Leu Gly Val Cys

35 40 45

Phe Ile Leu Leu Ala Arg Thr Ile Asp Gln Lys Val Lys Asn Ala Phe

50 55 60

Pro Ile Ala Ile Ile Trp Ile Thr Leu Thr Leu Phe Tyr Leu Asn Leu

65 70 75 80

Gly His Ile Ser Trp Arg Leu Ser Phe Trp Phe Ile Leu Leu Leu Leu

85 90 95

Gly Leu Leu Val Ile Lys Pro Thr Leu Tyr Lys Lys Gln Phe Ile Tyr

100 105 110

Ser Trp Glu Glu Arg Ile Lys Asp Gly Ile Ile Ile Val Ser Leu Met

115 120 125

Gly Val Leu Phe Tyr Ile Ala Gly Leu Leu Phe Pro Ile Arg Ala His

130 135 140

Ile Thr Gly Gly Ser Ile Glu Arg Leu His Tyr Ile Ile Ala Trp Glu

145 150 155 160

Pro Ile Ala Leu Ala Thr Leu Ile Leu Thr Leu Val Tyr Leu Cys Leu

165 170 175

Val Lys Ile Leu Gln Gly Lys Ser Cys Gln Ile Gly Asp Val Phe Asn

180 185 190

Val Asp Arg Tyr Lys Lys Leu Leu Gln Ala Tyr Gly Gly Ser Ser Asp

195 200 205

Ser Gly Leu Ala Phe Leu Asn Asp Lys Arg Leu Tyr Trp Tyr Gln Lys

210 215 220

Asn Gly Glu Asp Cys Val Ala Phe Gln Phe Val Ile Val Asn Asn Lys

225 230 235 240

Cys Leu Ile Met Gly Glu Pro Ala Gly Asp Asp Thr Tyr Ile Arg Glu

245 250 255

Ala Ile Glu Ser Phe Ile Asp Asp Ala Asp Lys Leu Asp Tyr Asp Leu

260 265 270

Val Phe Tyr Ser Ile Gly Gln Lys Leu Thr Leu Leu Leu His Glu Tyr

275 280 285

Gly Phe Asp Phe Met Lys Val Gly Glu Asp Ala Leu Val Asn Leu Glu

290 295 300

Thr Phe Thr Leu Lys Gly Asn Lys Tyr Lys Pro Phe Arg Asn Ala Leu

305 310 315 320

Asn Arg Val Glu Lys Asp Gly Phe Tyr Phe Glu Val Val Gln Ser Pro

325 330 335

His Ser Gln Glu Leu Leu Asn Ser Leu Glu Glu Ile Ser Asn Thr Trp

340 345 350

Leu Glu Gly Arg Pro Glu Lys Gly Phe Ser Leu Gly Tyr Phe Asn Lys

355 360 365

Asp Tyr Phe Gln Gln Ala Pro Ile Ala Leu Val Lys Asn Ala Glu His

370 375 380

Glu Val Val Ala Phe Ala Asn Ile Met Pro Asn Tyr Glu Lys Ser Ile

385 390 395 400

Ile Ser Ile Asp Leu Met Arg His Asp Lys Gln Lys Ile Pro Asn Gly

405 410 415

Val Met Asp Phe Leu Phe Leu Ser Leu Phe Ser Tyr Tyr Gln Glu Lys

420 425 430

Gly Tyr His Tyr Phe Asp Leu Gly Met Ala Pro Leu Ser Gly Val Gly

435 440 445

Arg Val Glu Thr Ser Phe Ala Lys Glu Arg Met Ala Tyr Leu Val Tyr

450 455 460

His Phe Gly Ser His Phe Tyr Ser Phe Asn Gly Leu His Lys Tyr Lys

465 470 475 480

Lys Lys Phe Thr Pro Leu Trp Ser Glu Arg Tyr Ile Ser Cys Ser Arg

485 490 495

Ser Ser Trp Leu Ile Cys Ala Ile Cys Ala Leu Leu Met Glu Asp Ser

500 505 510

Lys Ile Lys Ile Val Lys

515

<210>7

<211>5126

<212>DNA

<213>链球菌

<220>

<221>CDS

<222>(1)...(687)

<221>CDS

<222>(701)...(2557)

<221>CDS

<222>(2566)...(3036)

<221>CDS

<222>(3106)...(4842)

<221>CDS

<222>(4850)...(5125)

<400>7

aat ttt gat atc gaa aca aca act ttt gag gca atg aaa aag cac gcg 48

Asn Phe Asp Ile Glu Thr Thr Thr Phe Glu Ala Met Lys Lys His Ala

1 5 10 15

tca tta ttg gag aaa ata tct gtt gag cgt tct ttt att gaa ttt gat 96

Ser Leu Leu Glu Lys Ile Ser Val Glu Arg Ser Phe Ile Glu Phe Asp

20 25 30

aaa ctt cta tta gca cct tat tgg cgt aaa gga atg ctg gca cta ata 144

Lys Leu Leu Leu Ala Pro Tyr Trp Arg Lys Gly Met Leu Ala Leu Ile

35 40 45

gat agt cat gct ttt aat tat cta cca tgc tta aaa aat agg gaa tta 192

Asp Ser His Ala Phe Asn Tyr Leu Pro Cys Leu Lys Asn Arg Glu Leu

50 55 60

caa tta agc gcc ttt ttg tcc cag tta gat aaa gat ttt tta ttt gag 240

Gln Leu Ser Ala Phe Leu Ser Gln Leu Asp Lys Asp Phe Leu Phe Glu

65 70 75 80

aca tca gaa caa gct tgg gca tca ctc atc ttg agt atg gaa gtt gaa 288

Thr Ser Glu Gln Ala Trp Ala Ser Leu Ile Leu Ser Met Glu Val Glu

85 90 95

cac aca aag act ttt tta aaa aaa tgg aag aca tca act cac ttt caa 336

His Thr Lys Thr Phe Leu Lys Lys Trp Lys Thr Ser Thr His Phe Gln

100 105 110

aaa gat gtt gag cat ata gtg gat gtt tat cgt att cgt gaa caa atg 384

Lys Asp Val Glu His Ile Val Asp Val Tyr Arg Ile Arg Glu Gln Met

115 120 125

gga ttg gct aaa gaa cat ctt tat cgt tat gga aaa act ata ata aaa 432

Gly Leu Ala Lys Glu His Leu Tyr Arg Tyr Gly Lys Thr Ile Ile Lys

130 135 140

caa gcg gaa ggt atc cgc aaa gca aga ggc ttg atg gtt gat ttc gaa 480

Gln Ala Glu Gly Ile Arg Lys Ala Arg Gly Leu Met Val Asp Phe Glu

145 150 155 160

aaa ata gaa caa cta gat agt gag tta gca atc cat gat agg cat gag 528

Lys Ile Glu Gln Leu Asp Ser Glu Leu Ala Ile His Asp Arg His Glu

165 170 175

ata gtt gtc aac ggt ggc acc tta atc aag aaa tta gga ata aaa cct 576

Ile Val Val Asn Gly Gly Thr Leu Ile Lys Lys Leu Gly Ile Lys Pro

180 185 190

ggt cca cag atg gga gat att atc tct caa att gaa tta gcc att gtt 624

Gly Pro Gln Met Gly Asp Ile Ile Ser Gln Ile Glu Leu Ala Ile Val

195 200 205

tta gga caa ctg att aat gaa gaa gag gct att tta cat ttt gtt aag 672

Leu Gly Gln Leu Ile Asn Glu Glu Glu Ala Ile Leu His Phe Val Lys

210 215 220

cag tac ttg atg gat tagagaggat tat atg agc gat ttt tta gta gat 721

Gln Tyr Leu Met Asp Met Ser Asp Phe Leu Val Asp

225 230 235

gga ttg act aag tcg gtt ggt gat aag acg gtc ttt agt aat gtt tca 769

Gly Leu Thr Lys Ser Val Gly Asp Lys Thr Val Phe Ser Asn Val Ser

240 245 250

ttt atc atc cat agt tta gac cgt att ggg att att ggt gtc aat gga 817

Phe Ile Ile His Ser Leu Asp Arg Ile Gly Ile Ile Gly Val Asn Gly

255 260 265

act gga aag aca aca cta tta gat gtt att tcg ggt gaa tta ggt ttt 865

Thr Gly Lys Thr Thr Leu Leu Asp Val Ile Ser Gly Glu Leu Gly Phe

270 275 280

gat ggt gat cgt tcc cct ttt tca tca gct aat gat tat aag att gct 913

Asp Gly Asp Arg Ser Pro Phe Ser Ser Ala Asn Asp Tyr Lys Ile Ala

285 290 295 300

tat tta aaa caa gaa cca gac ttt gat gat tct cag aca att ttg gac 961

Tyr Leu Lys Gln Glu Pro Asp Phe Asp Asp Ser Gln Thr Ile Leu Asp

305 310 315

acc gta ctt tct tct gac tta aga gag atg gct tta att aaa gaa tat 1009

Thr Val Leu Ser Ser Asp Leu Arg Glu Met Ala Leu Ile Lys Glu Tyr

320 325 330

gaa tta ttg ctt aat cac tac gaa gaa agt aag caa tca cgt cta gag 1057

Glu Leu Leu Leu Asn His Tyr Glu Glu Ser Lys Gln Ser Arg Leu Glu

335 340 345

aaa gta atg gca gaa atg gat tct tta gat gct tgg tct att gag agc 1105

Lys Val Met Ala Glu Met Asp Ser Leu Asp Ala Trp Ser Ile Glu Ser

350 355 360

gaa gtc aaa aca gta tta tcc aaa tta ggt att act gat ttg cag ttg 1153

Glu Val Lys Thr Val Leu Ser Lys Leu Gly Ile Thr Asp Leu Gln Leu

365 370 375 380

tcg gtt ggt gaa tta tca gga gga tta cga aga cgt gtt caa tta gcg 1201

Ser Val Gly Glu Leu Ser Gly Gly Leu Arg Arg Arg Val Gln Leu ALa

385 390 395

caa gta tta tta aat gat gca gat tta ttg ctc tta gac gaa cct act 1249

Gln Val Leu Leu Asn Asp Ala Asp Leu Leu Leu Leu Asp Glu Pro Thr

400 405 410

aac cac tta gat att gac act att gca tgg tta acg aat ttt ttg aaa 1297

Asn His Leu Asp Ile Asp Thr Ile Ala Trp Leu Thr Asn Phe Leu Lys

415 420 425

aat agt aaa aag aca gtg ctt ttt ata act cat gat cgt tat ttt cta 1345

Asn Ser Lys Lys Thr Val Leu Phe Ile Thr His Asp Arg Tyr Phe Leu

430 435 440

gac aat gtt gca aca cgt att ttt gaa tta gat aag gca cag att aca 1393

Asp Asn Val Ala Thr Arg Ile Phe Glu Leu Asp Lys Ala Gln Ile Thr

445 450 455 460

gaa tat caa ggc aat tat cag gat tat gtc cga ctt cgt gca gaa caa 1441

Glu Tyr Gln Gly Asn Tyr Gln Asp Tyr Val Arg Leu Arg Ala Glu Gln

465 470 475

gac gag cgt gat gct gct agt tta cat aaa aag aaa cag ctt tat aaa 1489

Asp Glu Arg Asp Ala Ala Ser Leu His Lys Lys Lys Gln Leu Tyr Lys

480 485 490

cag gaa cta gct tgg atg cgt act cag cca caa gct cgt gca acg aaa 1537

Gln Glu Leu Ala Trp Met Arg Thr Gln Pro Gln Ala Arg Ala Thr Lys

495 500 505

caa cag gct cgt att aat cgt ttt caa aat cta aaa aac gat tta cac 1585

Gln Gln Ala Arg Ile Asn Arg Phe Gln Asn Leu Lys Asn Asp Leu His

510 515 520

caa aca agc gat aca agc gat ttg gaa atg aca ttt gaa aca agt cga 1633

Gln Thr Ser Asp Thr Ser Asp Leu Glu Met Thr Phe Glu Thr Ser Arg

525 530 535 540

att ggg aaa aag gtt att aat ttt gaa aat gtc tct ttt tct tac cca 1681

Ile Gly Lys Lys Val Ile Asn Phe Glu Asn Val Ser Phe Ser Tyr Pro

545 550 555

gat aaa tct atc ttg aaa gac ttt aat ttg tta att caa aat aaa gac 1729

Asp Lys Ser Ile Leu Lys Asp Phe Asn Leu Leu Ile Gln Asn Lys Asp

560 565 570

cgt att ggc atc gtt gga gat aat ggt gtt gga aag tca acc tta ctt 1777

Arg Ile Gly Ile Val Gly Asp Asn Gly Val Gly Lys Ser Thr Leu Leu

575 580 585

aat tta att gtt caa gat tta cag ccg gat tcg ggt aat gtc tct att 1825

Asn Leu Ile Val Gln Asp Leu Gln Pro Asp Ser Gly Asn Val Ser Ile

590 595 600

ggt gaa acg ata cgt gta ggt tac ttt tca caa caa ctt cat aat atg 1873

Gly Glu Thr Ile Arg Val Gly Tyr Phe Ser Gln Gln Leu His Asn Met

605 610 615 620

gat ggc tca aaa cgt gtt att aat tat ttg caa gag gtt gca gat gag 1921

Asp Gly Ser Lys Arg Val Ile Asn Tyr Leu Gln Glu Val Ala Asp Glu

625 630 635

gtt aaa act agt gtc ggt aca aca agt gtg aca gaa cta ttg gaa caa 1969

Val Lys Thr Ser Val Gly Thr Thr Ser Val Thr Glu Leu Leu Glu Gln

640 645 650

ttt ctc ttt cca cgt tcg aca cat gga aca caa att gca aaa tta tca 2017

Phe Leu Phe Pro Arg Ser Thr His Gly Thr Gln Ile Ala Lys Leu Ser

655 660 665

ggt ggt gag aaa aaa aga ctt tac ctt tta aaa atc ctg att gaa aag 2065

Gly Gly Glu Lys Lys Arg Leu Tyr Leu Leu Lys Ile Leu Ile Glu Lys

670 675 680

cct aat gtg tta cta ctt gat gag ccg aca aat gac tta gat att gct 2113

Pro Asn Val Leu Leu Leu Asp Glu Pro Thr Asn Asp Leu Asp Ile Ala

685 690 695 700

aca tta act gtt ctt gaa aat ttt tta caa ggc ttt ggt ggt cct gtg 2161

Thr Leu Thr Val Leu Glu Asn Phe Leu Gln Gly Phe Gly Gly Pro Val

705 710 715

att aca gtt agt cac gat cgt tac ttt tta gat aaa gtg gct aat aaa 2209

Ile Thr Val Ser His Asp Arg Tyr Phe Leu Asp Lys Val Ala Asn Lys

720 725 730

att att gcg ttt gaa gat aac gat atc cgt gaa ttt ttt ggt aat tat 2257

Ile Ile Ala Phe Glu Asp Asn Asp Ile Arg Glu Phe Phe Gly Asn Tyr

735 740 745

act gat tat tta gat gaa aaa gca ttt aat gag caa aat aat gaa gtt 2305

Thr Asp Tyr Leu Asp Glu Lys Ala Phe Asn Glu Gln Asn Asn Glu Val

750 755 760

atc agt aaa aaa gag agt acc aag aca agt cgt gaa aag caa agt cgt 2353

Ile Ser Lys Lys Glu Ser Thr Lys Thr Ser Arg Glu Lys Gln Ser Arg

765 770 775 780

aaa aga atg tct tac ttt gaa aaa caa gaa tgg gcg aca att gaa gac 2401

Lys Arg Met Ser Tyr Phe Glu Lys Gln Glu Trp Ala Thr Ile Glu Asp

785 790 795

gat att atg ata ttg gaa aat act atc act cgt ata gaa aat gat atg 2449

Asp Ile Met Ile Leu Glu Asn Thr Ile Thr Arg Ile Glu Asn Asp Met

800 805 810

caa aca tgt ggt agt gat ttt aca agg tta tct gat tta caa aag gaa 2497

Gln Thr Cys Gly Ser Asp Phe Thr Arg Leu Ser Asp Leu Gln Lys Glu

815 820 825

tta gat gca aaa aat gaa gca ctt cta gaa aag tat gac cgt tat gag 2545

Leu Asp Ala Lys Asn Glu Ala Leu Leu Glu Lys Tyr Asp Arg Tyr Glu

830 835 840

tac ctt agt gag ttagacac atg att atc cgt ccg att att aaa aat gat 2595

Tyr Leu Ser Glu LeuAspThrMet Ile Ile Arg Pro Ile Ile Lys Asn Asp

845 850 855 860

gac caa gca gtt gca caa tta att cga caa agt tta cgc gcc tat gat 2643

Asp Gln Ala Val Ala Gln Leu Ile Arg Gln Ser Leu Arg Ala Tyr Asp

865 870 875

tta gat aaa cct gat aca gca tat tca gac cct cac tta gat cat ttg 2691

Leu Asp Lys Pro Asp Thr Ala Tyr Ser Asp Pro His Leu Asp His Leu

880 885 890

acc tca tac tac gaa aaa ata gag aag tca gga ttc ttt gtc att gag 2739

Thr Ser Tyr Tyr Glu Lys Ile Glu Lys Ser Gly Phe Phe Val Ile Glu

895 900 905

gag aga gat gag att att ggc tgt ggc ggc ttt ggt ccg ctg aaa aat 2787

Glu Arg Asp Glu Ile Ile Gly Cys Gly Gly Phe Gly Pro Leu Lys Asn

910 915 920 925

cta att gca gag atg cag aag gtg tac att gca gaa cgt ttc cgt ggt 2835

Leu Ile Ala Glu Met Gln Lys Val Tyr Ile Ala Glu Arg Phe Arg Gly

930 935 940

aag ggg ctt gct act gat tta gtg aaa atg att gaa gta gaa gct cga 2883

Lys Gly Leu Ala Thr Asp Leu Val Lys Met Ile Glu Val Glu Ala Arg

945 950 955

aaa att ggg tat aga caa ctt tat tta gag aca gcc agt act ttg agt 2931

Lys Ile Gly Tyr Arg Gln Leu Tyr Leu Glu Thr Ala Ser Thr Leu Ser

960 965 970

agg gca act gcg gtt tat aag cat atg gga tat tgt gcc tta tcg caa 2979

Arg Ala Thr Ala Val Tyr Lys His Met Gly Tyr Cys Ala Leu Ser Gln

975 980 985

cca ata gca aat gat caa ggt cat aca gct atg gat att tgg atg att 3027

Pro Ile Ala Asn Asp Gln Gly His Thr Ala Met Asp Ile Trp Met Ile

990 995 1000 1005

aaa gat tta taagttgaaa gtggattagt gaacatggat taattatttt 3076

Lys Asp Leu

gagataagag gaaagaaaag gagacatat atg gca tat att tgg tct tat ttg 3129

Met Ala Tyr Ile Trp Ser Tyr Leu

1010 1015

aaa agg tac ccc aat tgg tta tgg ctt gat tta cta gga gct atg ctt 3177

Lys Arg Tyr Pro Asn Trp Leu Trp Leu Asp Leu Leu Gly Ala Met Leu

1020 1025 1030

ttt gtg acg gtt atc cta gga atg ccc aca gcc tta gcg ggt atg att 3225

Phe Val Thr Val Ile Leu Gly Met Pro Thr Ala Leu Ala Gly Met Ile

1035 1040 1045

gat aat ggc gtt aca aaa ggt gat cgg act gga gtt tat ctg tgg acg 3273

Asp Asn Gly Val Thr Lys Gly Asp Arg Thr Gly Val Tyr Leu Trp Thr

1050 1055 1060

ttc atc atg ttt ata ttt gtt gta cta ggt att att ggg cgt att acg 3321

Phe Ile Met Phe Ile Phe Val Val Leu Gly Ile Ile Gly Arg Ile Thr

1065 1070 1075 1080

atg gct tac gca tct agt cgc tta acg aca aca atg att aga gat atg 3369

Met Ala Tyr Ala Ser Ser Arg Leu Thr Thr Thr Met Ile Arg Asp Met

1085 1090 1095

cgt aat gat atg tat gct aag ctt caa gaa tac tcc cat cat gaa tat 3417

Arg Asn Asp Met Tyr Ala Lys Leu Gln Glu Tyr Ser His His Glu Tyr

1100 1105 1110

gaa cag ata ggt gta tct tca cta gtg aca cgt atg aca agc gat act 3465

Glu Gln Ile Gly Val Ser Ser Leu Val Thr Arg Met Thr Ser Asp Thr

1115 1120 1125

ttt gtt ttg atg caa ttt gct gaa atg tct tta cgt tta ggc cta gta 3513

Phe Val Leu Met Gln Phe Ala Glu Met Ser Leu Arg Leu Gly Leu Val

1130 1135 1140

act cct atg gta atg att ttt agc gtg gtt atg ata cta att acg agt 3561

Thr Pro Met Val Met Ile Phe Ser Val Val Met Ile Leu Ile Thr Ser

1145 1150 1155 1160

cca tct ttg gct tgg ctt gta gcg gtt gcg atg cct ctt ttg gta gga 3609

Pro Ser Leu Ala Trp Leu Val Ala Val Ala Met Pro Leu Leu Val Gly

1165 1170 1175

gtc gtt tta tat gta gct ata aaa aca aaa cct tta tct gaa aga caa 3657

Val Val Leu Tyr Val Ala Ile Lys Thr Lys Pro Leu Ser Glu Arg Gln

1180 1185 1190

cag act atg ctt gat aaa atc aat caa tat gtt cgt gaa aat tta aca 3705

Gln Thr Met Leu Asp Lys Ile Asn Gln Tyr Val Arg Glu Asn Leu Thr

1195 1200 1205

ggg tta cgc gtt gtt aga gcc ttt gca aga gag aat ttt caa tca caa 3753

Gly Leu Arg Val Val Arg Ala Phe Ala Arg Glu Asn Phe Gln Ser Gln

1210 1215 1220

aaa ttt caa gtc gct aac caa cgt tac aca gat act tca act ggt ctt 3801

Lys Phe Gln Val Ala Asn Gln Arg Tyr Thr Asp Thr Ser Thr Gly Leu

1225 1230 1235 1240

ttt aaa tta aca ggg cta aca gaa cca ctt ttc gtt caa att att att 3849

Phe Lys Leu Thr Gly Leu Thr Glu Pro Leu Phe Val Gln Ile Ile Ile

1245 1250 1255

gca atg att gtg gct atc gtt tgg ttt gct ttg gat ccc tta caa aga 3897

Ala Met Ile Val Ala Ile Val Trp Phe Ala Leu Asp Pro Leu Gln Arg

1260 1265 1270

ggt gct att aaa ata ggg gat tta gtt gct ttt atc gaa tat agc ttc 3945

Gly Ala Ile Lys Ile Gly Asp Leu Val Ala Phe Ile Glu Tyr Ser Phe

1275 1280 1285

cat gct ctc ttt tca ttt ttg cta ttt gcc aat ctt ttt act atg tat 3993

His Ala Leu Phe Ser Phe Leu Leu Phe Ala Asn Leu Phe Thr Met Tyr

1290 1295 1300

cct cgt atg gtg gta tca agc cat cgt att aga gag gtg atg gat atg 4041

Pro Arg Met Val Val Ser Ser His Arg Ile Arg Glu Val Met Asp Met

1305 1310 1315 1320

cca atc tct atc aat cct aat gcc gaa ggt gtt acg gat acg aaa ctt 4089

Pro Ile Ser Ile Asn Pro Asn Ala Glu Gly Val Thr Asp Thr Lys Leu

1325 1330 1335

aaa ggg cat tta gaa ttt gat aat gta aca ttc gct tat cca gga gaa 4137

Lys Gly His Leu Glu Phe Asp Asn Val Thr Phe Ala Tyr Pro Gly Glu

1340 1345 1350

aca gag agt ccc gtt ttg cat gat att tct ttt aaa gct aag cct gga 4185

Thr Glu Ser Pro Val Leu His Asp Ile Ser Phe Lys Ala Lys Pro Gly

1355 1360 1365

gaa aca att gct ttt att ggt tca aca ggt tca gga aaa tct tct ctt 4233

Glu Thr Ile Ala Phe Ile Gly Ser Thr Gly Ser Gly Lys Ser Ser Leu

1370 1375 1380

gtt aat ttg att cca cgt ttt tat gat gtg aca ctt gga aaa atc tta 4281

Val Asn Leu Ile Pro Arg Phe Tyr Asp Val Thr Leu Gly Lys Ile Leu

1385 1390 1395 1400

gta gat gga gtt gat gta aga gat tat aac ctt aaa tca ctt cgc caa 4329

Val Asp Gly Val Asp Val Arg Asp Tyr Asn Leu Lys Ser Leu Arg Gln

1405 1410 1415

aag att gga ttt atc ccc caa aaa gct ctt tta ttt aca ggg aca ata 4377

Lys Ile Gly Phe Ile Pro Gln Lys Ala Leu Leu Phe Thr Gly Thr Ile

1420 1425 1430

gga gag aat tta aaa tat gga aaa gct gat gct act att gat gat ctt 4425

Gly Glu Asn Leu Lys Tyr Gly Lys Ala Asp Ala Thr Ile Asp Asp Leu

1435 1440 1445

aga caa gcg gtt gat att tct caa gct aaa gag ttt att gag agt cac 4473

Arg Gln Ala Val Asp Ile Ser Gln Ala Lys Glu Phe Ile Glu Ser His

1450 1455 1460

caa gaa gcc ttt gaa acg cat tta gct gaa ggt ggg agc aat ctt tct 4521

Gln Glu Ala Phe Glu Thr His Leu Ala Glu Gly Gly Ser Asn Leu Ser

1465 1470 1475 1480

ggg ggt caa aaa caa cgg tta tct att gct agg gct gtt gtt aaa gat 4569

Gly Gly Gln Lys Gln Arg Leu Ser Ile Ala Arg Ala Val Val Lys Asp

1485 1490 1495

cca gat tta tat att ttt gat gat tca ttt tct gct ctc gat tat aag 4617

Pro Asp Leu Tyr Ile Phe Asp Asp Ser Phe Ser Ala Leu Asp Tyr Lys

1500 1505 1510

aca gac gct act tta aga gcg cgt cta aaa gaa gta acc ggt gat tct 4665

Thr Asp Ala Thr Leu Arg Ala Arg Leu Lys Glu Val Thr Gly Asp Ser

1515 1520 1525

aca gtt ttg ata gtt gct caa agg gtg ggt acg att atg gat gct gat 4713

Thr Val Leu Ile Val Ala Gln Arg Val Gly Thr Ile Met Asp Ala Asp

1530 1535 1540

cag att att gtc ctt gat gaa ggc gaa att gtc ggt cgt ggt acc cac 4761

Gln Ile Ile Val Leu Asp Glu Gly Glu Ile Val Gly Arg Gly Thr His

1545 1550 1555 1560

gct caa tta ata gaa aat aat gct att tat cgt gaa atc gct gag tca 4809

Ala Gln Leu Ile Glu Asn Asn Ala Ile Tyr Arg Glu Ile Ala Glu Ser

1565 1570 1575

caa ctg aag aac caa aac tta tca gaa gga gag tgattgt atg aga aaa 4858

Gln Leu Lys Asn Gln Asn Leu Ser Glu Gly Glu Met Arg Lys

1580 1585 1590

aaa tct gtt ttt ttg aga tta tgg tct tac cta act cgc tac aaa gct 4906

Lys Ser Val Phe Leu Arg Leu Trp Ser Tyr Leu Thr Arg Tyr Lys Ala

1595 1600 1605

act ctt ttc tta gcg att ttt ttg aaa gtt tta tct agt ttt atg agt 4954

Thr Leu Phe Leu Ala Ile Phe Leu Lys Val Leu Ser Ser Phe Met Ser

1610 1615 1620

gtt ctg gag cct ttt att tta ggg tta gcg ata aca gag ttg act gct 5002

Val Leu Glu Pro Phe Ile Leu Gly Leu Ala Ile Thr Glu Leu Thr Ala

1625 1630 1635

aac ctt gtt gat atg gct aag gga gtt tct ggg gca gaa ttg aac gtt 5050

Asn Leu Val Asp Met Ala Lys Gly Val Ser Gly Ala Glu Leu Asn Val

1640 1645 1650

cct tat att gct ggt att ttg att att tat ttt ttc aga ggt gtt ttc 5098

Pro Tyr Ile Ala Gly Ile Leu Ile Ile Tyr Phe Phe Arg Gly Val Phe

1655 1660 1665 1670

cat gaa tta ggt tct tat ggc tca aat t 5126

Tyr Clu Leu Gly Ser Tyr Gly Ser Asn

1675

<210>8

<211>229

<212>蛋白质

<213>链球菌

<400>8

Asn Phe Asp Ile Glu Thr Thr Thr Phe Glu Ala Met Lys Lys His Ala

1 5 10 15

Ser Leu Leu Glu Lys Ile Ser Val Glu Arg Ser Phe Ile Glu Phe Asp

20 25 30

Lys Leu Leu Leu Ala Pro Tyr Trp Arg Lys Gly Met Leu Ala Leu Ile

35 40 45

Asp Ser His Ala Phe Asn Tyr Leu Pro Cys Leu Lys Asn Arg Glu Leu

50 55 60

Gln Leu Ser Ala Phe Leu Ser Gln Leu Asp Lys Asp Phe Leu Phe Glu

65 70 75 80

Thr Ser Glu Gln Ala Trp Ala Ser Leu Ile Leu Ser Met Glu Val Glu

85 90 95

His Thr Lys Thr Phe Leu Lys Lys Trp Lys Thr Ser Thr His Phe Gln

100 105 110

Lys Asp Val Glu His Ile Val Asp Val Tyr Arg Ile Arg Glu Gln Met

115 120 125

Gly Leu Ala Lys Glu His Leu Tyr Arg Tyr Gly Lys Thr Ile Ile Lys

130 135 140

Gln Ala Glu Gly Ile Arg Lys Ala Arg Gly Leu Met Val Asp Phe Glu

145 150 155 160

Lys Ile Glu Gln Leu Asp Ser Glu Leu Ala Ile His Asp Arg His Glu

165 170 175

Ile Val Val Asn Gly Gly Thr Leu Ile Lys Lys Leu Gly Ile Lys Pro

180 185 190

Gly Pro Gln Met Gly Asp Ile Ile Ser Gln Ile Glu Leu Ala Ile Val

195 200 205

Leu Gly Gln Leu Ile Asn Glu Glu Glu Ala Ile Leu His Phe Val Lys

210 215 220

Gln Tyr Leu Met Asp

225

<210>9

<211>622

<212>PRT

<213>Streptococcus

<400>9

Met Ser Asp Phe Leu Val Asp Gly Leu Thr Lys Ser Val Gly Asp Lys

1 5 10 15

Thr Val Phe Ser Asn Val Ser Phe Ile Ile His Ser Leu Asp Arg Ile

20 25 30

Gly Ile Ile Gly Val Asn Gly Thr Gly Lys Thr Thr Leu Leu Asp Val

35 40 45

Ile Ser Gly Glu Leu Gly Phe Asp Gly Asp Arg Ser Pro Phe Ser Ser

50 55 60

Ala Asn Asp Tyr Lys Ile Ala Tyr Leu Lys Gln Glu Pro Asp Phe Asp

65 70 75 80

Asp Ser Gln Thr Ile Leu Asp Thr Val Leu Ser Ser Asp Leu Arg Glu

85 90 95

Met Ala Leu Ile Lys Glu Tyr Glu Leu Leu Leu Asn His Tyr Glu Glu

100 105 110

Ser Lys Gln Ser Arg Leu Glu Lys Val Met Ala Glu Met Asp Ser Leu

115 120 125

Asp Ala Trp Ser Ile Glu Ser Glu Val Lys Thr Val Leu Ser Lys Leu

130 135 140

Gly Ile Thr Asp Leu Gln Leu Ser Val Gly Glu Leu Ser Gly Gly Leu

145 150 155 160

Arg Arg Arg Val Gln Leu Ala Gln Val Leu Leu Asn Asp Ala Asp Leu

165 170 175

Leu Leu Leu Asp Glu Pro Thr Asn His Leu Asp Ile Asp Thr Ile Ala

180 185 190

Trp Leu Thr Asn Phe Leu Lys Asn Ser Lys Lys Thr Val Leu Phe Ile

195 200 205

Thr His Asp Arg Tyr Phe Leu Asp Asn Val Ala Thr Arg Ile Phe Glu

210 215 220

Leu Asp Lys Ala Gln Ile Thr Glu Tyr Gln Gly Asn Tyr Gln Asp Tyr

225 230 235 240

Val Arg Leu Arg Ala Glu Gln Asp Glu Arg Asp Ala Ala Ser Leu His

245 250 255

Lys Lys Lys Gln Leu Tyr Lys Gln Glu Leu Ala Trp Met Arg Thr Gln

260 265 270

Pro Gln Ala Arg Ala Thr Lys Gln Gln Ala Arg Ile Asn Arg Phe Gln

275 280 285

Asn Leu Lys Asn Asp Leu His Gln Thr Ser Asp Thr Ser Asp Leu Glu

290 295 300

Met Thr Phe Glu Thr Ser Arg Ile Gly Lys Lys Val Ile Asn Phe Glu

305 310 315 320

Asn Val Ser Phe Ser Tyr Pro Asp Lys Ser Ile Leu Lys Asp Phe Asn

325 330 335

Leu Leu Ile Gln Asn Lys Asp Arg Ile Gly Ile Val Gly Asp Asn Gly

340 345 350

Val Gly Lys Ser Thr Leu Leu Asn Leu Ile Val Gln Asp Leu Gln Pro

355 360 365

Asp Ser Gly Asn Val Ser Ile Gly Glu Thr Ile Arg Val Gly Tyr Phe

370 375 380

Ser Gln Gln Leu His Asn Met Asp Gly Ser Lys Arg Val Ile Asn Tyr

385 390 395 400

Leu Gln Glu Val Ala Asp Glu Val Lys Thr Ser Val Gly Thr Thr Ser

405 410 415

Val Thr Glu Leu Leu Glu Gln Phe Leu Phe Pro Arg Ser Thr His Gly

420 425 430

Thr Gln Ile Ala Lys Leu Ser Gly Gly Glu Lys Lys Arg Leu Tyr Leu

435 440 445

Leu Lys Ile Leu Ile Glu Lys Pro Asn Val Leu Leu Leu Asp Glu Pro

450 455 460

Thr Asn Asp Leu Asp Ile Ala Thr Leu Thr Val Leu Glu Asn Phe Leu

465 470 475 480

Gln Gly Phe Gly Gly Pro Val Ile Thr Val Ser His Asp Arg Tyr Phe

485 490 495

Leu Asp Lys Val Ala Asn Lys Ile Ile Ala Phe Glu Asp Asn Asp Ile

500 505 510

Arg Glu Phe Phe Gly Asn Tyr Thr Asp Tyr Leu Asp Glu Lys Ala Phe

515 520 525

Asn Glu Gln Asn Asn Glu Val Ile Ser Lys Lys Glu Ser Thr Lys Thr

530 535 540

Ser Arg Glu Lys Gln Ser Arg Lys Arg Met Ser Tyr Phe Glu Lys Gln

545 550 555 560

Glu Trp Ala Thr Ile Glu Asp Asp Ile Met Ile Leu Glu Asn Thr Ile

565 570 575

Thr Arg Ile Glu Asn Asp Met Gln Thr Cys Gly Ser Asp Phe Thr Arg

580 585 590

Leu Ser Asp Leu Gln Lys Glu Leu Asp Ala Lys Asn Glu Ala Leu Leu

595 600 605

Glu Lys Tyr Asp Arg Tyr Glu Tyr Leu Ser Glu Leu Asp Thr

610 615 620

<210>10

<211>157

<212>蛋白质

<213>链球菌

<400>10

Met Ile Ile Arg Pro Ile Ile Lys Asn Asp Asp Gln Ala Val Ala Gln

1 5 10 15

Leu Ile Arg Gln Ser Leu Arg Ala Tyr Asp Leu Asp Lys Pro Asp Thr

20 25 30

Ala Tyr Ser Asp Pro His Leu Asp His Leu Thr Ser Tyr Tyr Glu Lys

35 40 45

Ile Glu Lys Ser Gly Phe Phe Val Ile Glu Glu Arg Asp Glu Ile Ile

50 55 60

Gly Cys Gly Gly Phe Gly Pro Leu Lys Asn Leu Ile Ala Glu Met Gln

65 70 75 80

Lys Val Tyr Ile Ala Glu Arg Phe Arg Gly Lys Gly Leu Ala Thr Asp

85 90 95

Leu Val Lys Met Ile Glu Val Glu Ala Arg Lys Ile Gly Tyr Arg Gln

100 105 110

Leu Tyr Leu Glu Thr Ala Ser Thr Leu Ser Arg Ala Thr Ala Val Tyr

115 120 125

Lys His Met Gly Tyr Cys Ala Leu Ser Gln Pro Ile Ala Asn Asp Gln

130 135 140

Gly His Thr Ala Met Asp Ile Trp Met Ile Lys Asp Leu

145 150 155

<210>11

<211>579

<212>蛋白质

<213>链球菌

<400>11

Met Ala Tyr Ile Trp Ser Tyr Leu Lys Arg Tyr Pro Asn Trp Leu Trp

1 5 10 15

Leu Asp Leu Leu Gly Ala Met Leu Phe Val Thr Val Ile Leu Gly Met

20 25 30

Pro Thr Ala Leu Ala Gly Met Ile Asp Asn Gly Val Thr Lys Gly Asp

35 40 45

Arg Thr Gly Val Tyr Leu Trp Thr Phe Ile Met Phe Ile Phe Val Val

50 55 60

Leu Gly Ile Ile Gly Arg Ile Thr Met Ala Tyr Ala Ser Ser Arg Leu

65 70 75 80

Thr Thr Thr Met Ile Arg Asp Met Arg Asn Asp Met Tyr Ala Lys Leu

85 90 95

Gln Glu Tyr Ser His His Glu Tyr Glu Gln Ile Gly Val Ser Ser Leu

100 105 110

Val Thr Arg Met Thr Ser Asp Thr Phe Val Leu Met Gln Phe Ala Glu

115 120 125

Met Ser Leu Arg Leu Gly Leu Val Thr Pro Met Val Met Ile Phe Ser

130 135 140

Val Val Met Ile Leu Ile Thr Ser Pro Ser Leu Ala Trp Leu Val Ala

145 150 155 160

Val Ala Met Pro Leu Leu Val Gly Val Val Leu Tyr Val Ala Ile Lys

165 170 175

Thr Lys Pro Leu Ser Glu Arg Gln Gln Thr Met Leu Asp Lys Ile Asn

180 185 190

Gln Tyr Val Arg Glu Asn Leu Thr Gly Leu Arg Val Val Arg Ala Phe

195 200 205

Ala Arg Glu Asn Phe Gln Ser Gln Lys Phe Gln Val Ala Asn Gln Arg

210 215 220

Tyr Thr Asp Thr Ser Thr Gly Leu Phe Lys Leu Thr Gly Leu Thr Glu

225 230 235 240

Pro Leu Phe Val Gln Ile Ile Ile Ala Met Ile Val Ala Ile Val Trp

245 250 255

Phe Ala Leu Asp Pro Leu Gln Arg Gly Ala Ile Lys Ile Gly Asp Leu

260 265 270

Val Ala Phe Ile Glu Tyr Ser Phe His Ala Leu Phe Ser Phe Leu Leu

275 280 285

Phe Ala Asn Leu Phe Thr Met Tyr Pro Arg Met Val Val Ser Ser His

290 295 300

Arg Ile Arg Glu Val Met Asp Met Pro Ile Ser Ile Asn Pro Asn Ala

305 310 315 320

Glu Gly Val Thr Asp Thr Lys Leu Lys Gly His Leu Glu Phe Asp Asn

325 330 335

Val Thr Phe Ala Tyr Pro Gly Glu Thr Glu Ser Pro Val Leu His Asp

340 345 350

Ile Ser Phe Lys Ala Lys Pro Gly Glu Thr Ile Ala Phe Ile Gly Ser

355 360 365

Thr Gly Ser Gly Lys Ser Ser Leu Val Asn Leu Ile Pro Arg Phe Tyr

370 375 380

Asp Val Thr Leu Gly Lys Ile Leu Val Asp Gly Val Asp Val Arg Asp

385 390 395 400

Tyr Asn Leu Lys Ser Leu Arg Gln Lys Ile Gly Phe Ile Pro Gln Lys

405 410 415

Ala Leu Leu Phe Thr Gly Thr Ile Gly Glu Asn Leu Lys Tyr Gly Lys

420 425 430

Ala Asp Ala Thr Ile Asp Asp Leu Arg Gln Ala Val Asp Ile Ser Gln

435 440 445

Ala Lys Glu Phe Ile Glu Ser His Gln Glu Ala Phe Glu Thr His Leu

450 455 460

Ala Glu Gly Gly Ser Asn Leu Ser Gly Gly Gln Lys Gln Arg Leu Ser

465 470 475 480

Ile Ala Arg Ala Val Val Lys Asp Pro Asp Leu Tyr Ile Phe Asp Asp

485 490 495

Ser Phe Ser Ala Leu Asp Tyr Lys Thr Asp Ala Thr Leu Arg Ala Arg

500 505 510

Leu Lys Glu Val Thr Gly Asp Ser Thr Val Leu Ile Val Ala Gln Arg

515 520 525

Val Gly Thr Ile Met Asp Ala Asp Gln Ile Ile Val Leu Asp Glu Gly

530 535 540

Glu Ile Val Gly Arg Gly Thr His Ala Gln Leu Ile Glu Asn Asn Ala

545 550 555 560

Ile Tyr Arg Glu Ile Ala Glu Ser Gln Leu Lys Asn Gln Asn Leu Ser

565 570 575

Glu Gly Glu

<210>12

<211>92

<212>蛋白质

<213>链球菌

<400>12

Met Arg Lys Lys Ser Val Phe Leu Arg Leu Trp Ser Tyr Leu Thr Arg

1 5 10 15

Tyr Lys Ala Thr Leu Phe Leu Ala Ile Phe Leu Lys Val Leu Ser Ser

20 25 30

Phe Met Ser Val Leu Glu Pro Phe Ile Leu Gly Leu Ala Ile Thr Glu

35 40 45

Leu Thr Ala Asn Leu Val Asp Met Ala Lys Gly Val Ser Gly Ala Glu

50 55 60

Leu Asn Val Pro Tyr Ile Ala Gly Ile Leu Ile Ile Tyr Phe Phe Arg

65 70 75 80

Gly Val Phe Tyr Glu Leu Gly Ser Tyr Gly Ser Asn

85 90

<210>13

<211>5215

<212>DNA

<213>链球菌

<220>

<221>CDS

<222>(3)...(122)

<221>CDS

<222>(133)...(2511)

<221>CDS

<222>(367)...(2511)

<221>CDS

<222>(2946)...(2716)

<223>互补链

<221>CDS

<222>(3252)...(2995)

<223>互补链

<221>CDS

<222>(3676)...(3299)

<223>互补链

<221>CDS

<222>(4124)...(3837)

<223>互补链

<221>CDS

<222>(5214)...(4351)

<223>互补链

<400>13

aa ttt gga agt gct cta tca aca gtt gaa gta aag gag att att agt 47

Phe Gly Ser Ala Leu Ser Thr Val Glu Val Lys Glu Ile Ile Ser

1 5 10 15

gaa gaa aac ata tgg tta tat cgg ctc agt tgc tgc cat ttt act agc 95

Glu Glu Asn Ile Trp Leu Tyr Arg Leu Ser Cys Cys His Phe Thr Ser

20 25 30

tac tca tat tgg aag tta cca act tgg taagcatcat atg ggt cta gca 144

Tyr Ser Tyr Trp Lys Leu Pro Thr Trp Met Gly Leu Ala

35 40

aca aag gac aat cag att gcc tat att gat gac agc aaa ggt aag gca 192

Tnr Lys Asp Asn Gln Ile Ala Tyr Ile Asp Asp Ser Lys Gly Lys Ala

45 50 55 60

aaa gcc cct aaa aca aac aaa acg atg gat caa atc agt gct gaa gaa 240

Lys Ala Pro Lys Thr Ash Lys Thr Met Asp Gln Ile Ser Ala Glu Glu

65 70 75

ggc atc tct gct gaa cag atc gta gtc aaa att act gac caa ggc tat 288

Gly Ile Ser Ala Glu Gln Ile Val Val Lys Ile Thr Asp Gln Gly Tyr

80 85 90

gtg acc tca cac ggt gac cat tat cat ttt tac aat ggg aaa gtt cct 336

Val Thr Ser His Gly Asp His Tyr His Phe Tyr Asn Gly Lys Val Pro

95 100 105

tat gat gcg att att agt gaa gag ttg ttg atg acg gat cct aat tac 384

Tyr Asp Ala Ile Ile Ser Glu Glu Leu Leu Met Thr Asp Pro Asn Tyr

110 115 120

cgt ttt aaa caa tca gac gtt atc aat gaa arc tta gac ggt tac gtt 432

Arg Phe Lys Gln Ser Asp Val Ile Asn Glu Ile Leu Asp Gly Tyr Val

125 130 135 140

att aaa gtc aat ggc aac tat tat gtt tac ctc aag cca ggt agt aag 480

Ile Lys Val Asn Gly Asn Tyr Tyr Val Tyr Leu Lys Pro Gly Ser Lys

145 150 155

cgc aaa aac att cga acc aaa caa caa att gct gag caa gta gcc aaa 528

Arg Lys Asn Ile Arg Thr Lys Gln Gln Ile Ala Glu Gln Val Ala Lys

160 165 170

gga act aaa gaa gct aaa gaa aaa ggt tta gct caa gtg gcc cat ctc 576

Gly Thr Lys Glu Ala Lys Glu Lys Gly Leu Ala Gln Val Ala His Leu

175 180 185

agt aaa gaa gaa gtt gcg gca gtc aat gaa gca aaa aga caa gga cgc 624

Ser Lys Glu Glu Val Ala Ala Val Asn Glu Ala Lys Arg Gln Gly Arg

190 195 200

tat act aca gac gat ggc tat att ttt agt tcg aca gat atc att gat 672

Tyr Thr Thr Asp Asp Gly Tyr Ile Phe Ser Pro Thr Asp Ile Ile Asp

205 210 215 220

gat tta gga gat gct tat tta gta cct cat ggt aat cac tat cat tat 720

Asp Leu Gly Asp Ala Tyr Leu Val Pro His Gly Asn His Tyr His Tyr

225 230 235

att cct aaa aag gat ttg tct cca agt gag cta gct gct gca caa gcc 768

Ile Pro Lys Lys Asp Leu Ser Pro Ser Glu Leu Ala Ala Ala Gln Ala

240 245 250

tac tgg agt caa aaa caa ggt cga ggt gct aga ccg tct gat tac cgc 816

Tyr Trp Ser Gln Lys Gln Gly Arg Gly Ala Arg Pro Ser Asp Tyr Arg

255 260 265

ccg aca cca gcc cca ggt cgt agg aaa gcc cca att cct gat gtg acg 864

Pro Thr Pro Ala Pro Gly Arg Arg Lys Ala Pro Ile Pro Asp Val Thr

270 275 280

cct aac cct gga caa ggt cat cag cca gat aac ggt ggc tat cat cca 912

Pro Asn Pro Gly Gln Gly His Gln Pro Asp Asn Gly Gly Tyr His Pro

285 290 295 300

gcg cct cct agg cca aat gat gcg tca caa aac aaa cac caa aga gat 960

Ala Pro Pro Arg Pro Asn Asp Ala Ser Gln Asn Lys His Gln Arg Asp

305 310 315

gag ttt aaa gga aaa acc ttt aag gaa ctt tta gat caa cta cac cgt 1008

Glu Phe Lys Gly Lys Thr Phe Lys Glu Leu Leu Asp Gln Leu His Arg

320 325 330

ctt gat ttg aaa tac cgt cat gtg gaa gaa gat ggg ttg att ttt gaa 1056

Leu Asp Leu Lys Tyr Arg His Val Glu Glu Asp Gly Leu Ile Phe Glu

335 340 345

ccg act caa gtg atc aaa tca aac gct ttt ggg tat gtg gtg cct cat 1104

Pro Thr Gln Val Ile Lys Ser Asn Ala Phe Gly Tyr Val Val Pro His

350 355 360

gga gat cat tat cat att atc cca aga agt cag tta tca cct ctt gaa 1152

Gly Asp His Tyr His Ile Ile Pro Arg Ser Gln Leu Ser Pro Leu Glu

365 370 375 380

atg gaa tta gca gat cga tac tta gct ggc caa act gag gac aat gac 1200

Met Glu Leu Ala Asp Arg Tyr Leu Ala Gly Gln Thr Glu Asp Asn Asp

385 390 395

tca ggt tca gag cac tca aaa cca tca gat aaa gaa gtg aca cat acc 1248

Ser Gly Ser Glu His Ser Lys Pro Ser Asp Lys Glu Val Thr His Thr

400 405 410

ttt ctt ggt cat cgc atc aaa gct tac gga aaa ggc tta gat ggt aaa 1296

Phe Leu Gly His Arg Ile Lys Ala Tyr Gly Lys Gly Leu Asp Gly Lys

415 420 425

cca tat gat acg agc gat gct tat gtt ttt agt aaa gaa tcc att cat 1344

Pro Tyr Asp Thr Ser Asp Ala Tyr Val Phe Ser Lys Glu Ser Ile His

430 435 440

tca gtg gat aaa tca gga gtt aca gct aaa cac gga gat cat ttc cac 1392

Ser Val Asp Lys Ser Gly Val Thr Ala Lys His Gly Asp His Phe His

445 450 455 460

tat ata gga ttt gga gaa ctt gaa caa tat gag ttg gat gag gtc gct 1440

Tyr Ile Gly Phe Gly Glu Leu Glu Gln Tyr Glu Leu Asp Glu Val Ala

465 470 475

aac tgg gtg aaa gca aaa ggt caa gct gat gag ctt gct gct gct ttg 1488

Asn Trp Val Lys Ala Lys Gly Gln Ala Asp Glu Leu Ala Ala Ala Leu

480 485 490

gat cag gaa caa ggc aaa gaa aaa cca ctc ttt gac act aaa aaa gtg 1536

Asp Gln Glu Gln Gly Lys Glu Lys Pro Leu Phe Asp Thr Lys Lys Val

495 500 505

agt cgc aaa gta aca aaa gat ggt aaa gtg ggc tat atg atg cca aaa 1564

Ser Arg Lys Val Thr Lys Asp Gly Lys Val Gly Tyr Met Met Pro Lys

510 515 520

gat ggt aag gac tat ttc tat gct cgt gat caa ctt gat ttg act cag 1632

Asp Gly Lys Asp Tyr Phe Tyr Ala Arg Asp Gln Leu Asp Leu Thr Gln

525 530 535 540

att gcc ttt gcc gaa caa gaa cta atg ctt aaa gat aag aag cat tac 1680

Ile Ala Phe Ala Glu Gln Glu Leu Met Leu Lys Asp Lys Lys His Tyr

545 550 555

cgt tat gac att gtt gac aca ggt att gag cca cga ctt gct gta gat 1728

Arg Tyr Asp Ile Val Asp Thr Gly Ile Glu Pro Arg Leu Ala Val Asp

560 565 570

gtg tca agt ctg ccg atg cat gct ggt aat gct act tac gat act gga 1776

Val Ser Ser Leu Pro Met His Ala Gly Asn Ala Thr Tyr Asp Thr Gly

575 580 585

agt tcg ttt gtt atc cca cat att gat cat atc cat gtc gtt ccg tat 1824

Ser Ser Phe Val Ile Pro His Ile Asp His Ile His Val Val Pro Tyr

590 595 600

tca tgg ttg acg cgc gat cag att gca aca gtc aag tat gtg atg caa 1872

Ser Trp Leu Thr Arg Asp Gln Ile Ala Thr Val Lys Tyr Val Met Gln

605 610 615 620

cac ccc gaa gtt cgt ccg gat gta tgg tct aag cca ggg cat gaa gag 1920

His Pro Glu Val Arg Pro Asp Val Trp Ser Lys Pro Gly His Glu Glu

625 630 635

tca ggt tcg gtc att cca aat gtt acg cct ctt gat aaa cgt gct ggt 1968

Ser Gly Ser Val Ile Pro Asn Val Thr Pro Leu Asp Lys Arg Ala Gly

640 645 650

atg cca aac tgg caa att atc cat tct gct gaa gaa gtt caa aaa gcc 2016

Met Pro Asn Trp Gln Ile Ile His Ser Ala Glu Glu Val Gln Lys Ala

655 660 665

cta gca gaa ggt cgt ttt gca aca cca gac ggc tat att ttc gat cca 2064

Leu Ala Glu Gly Arg Phe Ala Thr Pro Asp Gly Tyr Ile Phe Asp Pro

670 675 680

cga gat gtt ttg gcc aaa gaa act ttt gta tgg aaa gat ggc tcc ttt 2112

Arg Asp Val Leu Ala Lys Glu Thr Phe Val Trp Lys Asp Gly Ser Phe

685 690 695 700

agc atc cca aga gca gat ggc agt tca ttg aga acc att aat aaa tct 2160

Ser Ile Pro Arg Ala Asp Gly Ser Ser Leu Arg Thr Ile Asn Lys Ser

705 710 715

gat cta tcc caa gct gag tgg caa caa gct caa gag tta ttg gca aag 2208

Asp Leu Ser Gln Ala Glu Trp Gln Gln Ala Gln Glu Leu Leu Ala Lys

720 725 730

aaa aat act ggt gat gct act gat acg gat aaa ccc aaa gaa aag caa 2256

Lys Asn Thr Gly Asp Ala Thr Asp Thr Asp Lys Pro Lys Glu Lys Gln

735 740 745

cag gca gat aag agc aat gaa aac caa cag cca agt gaa gcc agt aaa 2304

Gln Ala Asp Lys Ser Asn Glu Asn Gln Gln Pro Ser Glu Ala Ser Lys

750 755 760

gaa gaa aaa gaa tca gat gac ttt ata gac agt tta cca gac tat ggt 2352

Glu Glu Lys Glu Ser Asp Asp Phe Ile Asp Ser Leu Pro Asp Tyr Gly

765 770 775 780

cta gat aga gca acc cra gaa gat cat atc aat caa tta gca caa aaa 2400

Leu Asp Arg Ala Thr Leu Glu Asp His Ile Asn Gln Leu Ala Gln Lys

785 790 795

gct aat atc gat cct aag tat ctc att ttc caa cca gaa ggt gtc caa 2448

Ala Asn Ile Asp Pro Lys Tyr Leu Ile Phe Gln Pro Glu Gly Val Gln

800 805 810

ttt tat aat aaa aat ggt gaa ttg gta act tat gat atc aag aca ctt 2496

Phe Tyr Asn Lys Asn Gly Glu Leu Val Thr Tyr Asp Ile Lys Thr Leu

815 820 825

caa caa ata aac cct taaccaaaag aagatctcat tgttaaagca ctgctttgtc 2551

Gln Gln Ile Asn Pro

830

aaagcaagtt acggtgattt tgaagtcatt ctatgtaacg agtagtgata aaagttggat 2611

aatagcggtt ttcttttgca aagaaatggt atccatgtta gaatagtaaa aaaagaggag 2671

gattcttgga ctaatgtcaa ataagtagac agaaaactgt gttattttattgcgt 2726

taaaataatt ttcttctttc tgattagggg ttagtcctag attagccgta tgtgggttgt 2786

aattgttata aaaattctca atgtattcaa agcagtctaa ttgaacctgt ttgatatttt 2846

gataatgttt tcggttgatt tgtctatgct ttaaatactt gaaaaatgct tcagttacgg 2906

cattatcata aggatatcca ggattagaaa aagaatgcat gatattggca ctgcacccta 2966

atagtgagac gcaagaaaaa cacttttaggcaatcagtt ttctgtactg tacaggcgac 3025

tggtcgttta atctctgttg aattctagtt tcattataaa atgtaatgta atttttaaca 3085

atatttgtta tactatcttt gttgtatttt ctcctattat ggaaataaaa ggtttcagtc 3145

tttaggacgg tgtgaaacca ttcaatacag gcattatctg caggtgttcc ttttcgagac 3205

attgagcgga taatgtcttt ttccgtgcaa gcctggtagt aagccataga agtatacact 3265

gagccttggt cactgtgtaa gattgctcct ttatttaggcaatt ttaactgatt 3319

aagggtgtct agtacaaaat ccgtgtcctg acaatctgag atagtgtaag ctataatttc 3379

tcggttatag agattcataa ttgatgagag atacaattta cagttaccga aatataggta 3439

ggtaatatct gttacgagct tttccttagg cttatcggca tggaaatccc gactcaattt 3499

attatctgtt aaataataag ctttacccaa attgggaact ttcttggtac gtgtccgaca 3559

aagccagcca ttatttttca tgatacgata gactttcttt gtattaacag tcaatccgtg 3619

gatttttttg agcaatcgtg taatggtacg atagccataa ataaagtgat tctccataca 3679

gagctgttca attaattcaa taaggtcatc tttttttgcg gcttctcata ctcctttttc 3739

caacggtaat aggtcgaccg cttgacctta aaacagtcta gaatgaaaac tatcgggtag 3799

ttgtttttat agtcttccac aagcttgata agacttactttatcgatt tccttatcaa 3857

gcctcgatac ttttttaaga ggtcaacctg taattgtaat tgttccactt cagacagatg 3917

ttccaagcct ttaccgtagg tatattgctt gccaacacct tgatgaaaac gataaagctc 3977

ctcgttttcg taccatttca tccaagtata gatttgacta ttatttttga tgcctaaagt 4037

ctccataata actctgttag acttgcctgc tttcttcata tcgatgcaag ccagcttagt 4097

ttcccatgaa tatgcttttt taaccataat aaaacattcc tgtttctagt ttactaaatt 4157

tcaacaggag tgcttttctt ttgtctcatt ttagggattc agtgcctatt gttgtcatca 4217

attatttttc taaattcccc ggacttaaat tgtgaccctt ggtcggaatg aaagagaagt 4277

gttccttcaa tctttctttt attaagcgaa aaggcaacac ttttctgtac aacatttata 4337

aagtgttttt ctaggcaattaatc ttttagtcat tggtgtttgg tagttgagac 4391

taccatgaat gcggtggtaa ttccaccaat gaacatagtc tttagtctta agagctagtt 4451

cttccagcaa ttgaaaggtt tcttgataaa caaattcaat tttgaaagca cgatacgtac 4511

tttcagctac ggcattgtca taaggataac cagcctgact aagcgaacgt gtgattccaa 4571

aggcttccaa tatttcatca attaactgat tatcaaactc tttgccacga tctgaatgga 4631

acatcttgac tttggtcagg gcgtaaggga tgctttgtat ggcttgctta acgagttcag 4691

cggtcttgtg ccaaccaaga gacaggccga tgatttcacg gttgtatagg tcaatgatga 4751

ggcaaacata agcccaacga ttgcctacac gaacataggt taagtcagtg actaaggctt 4811

gtagtggtct ttcttgctta aattgcctgt ctaagtggtt gggaataggg gcttcattct 4871

tgcctctaga atgtggtttg aaggtggctt tctgataaac agaaaccaaa ttgagtcgct 4931

tcataatgcg tcgaatccga cgacgtgaaa gtgtgatacc ttcgttattc aagcatattt 4991

tgatttttct ggatccgtat ctagactcgc tatcgagaaa aattctttta atagtttctt 5051

caaactccgt ttcagatact gactccacgg cttgatagta ataacttgag tgtggcatat 5111

tcagccagcg acacatcttt gaaatgctgt atttatcctt attagcagtg attatttccc 5171

tttttgtgcc ataatcaccg ctgcttgctt taggatatct aatt 5215

<210>14

<211>40

<212>蛋白质

<213>链球菌

<400>14

Phe Gly Ser Ala Leu Ser Thr Val Glu Val Lys Glu Ile Ile Ser Glu

1 5 10 15

Glu Asn Ile Trp Leu Tyr Arg Leu Ser Cys Cys His Phe Thr Ser Tyr

20 25 30

Ser Tyr Trp Lys Leu Pro Thr Trp

35 40

<210>15

<211>793

<212>蛋白质

<213>链球菌

<400>15

Met Gly Leu Ala Thr Lys Asp Asn Gln Ile Ala Tyr Ile Asp Asp Ser

1 5 10 15

Lys Gly Lys Ala Lys Ala Pro Lys Thr Asn Lys Thr Met Asp Gln Ile

20 25 30

Ser Ala Glu Glu Gly Ile Ser Ala Glu Gln Ile Val Val Lys Ile Thr

35 40 45

Asp Gln Gly Tyr Val Thr Ser His Gly Asp His Tyr His Phe Tyr Asn

50 55 60

Gly Lys Val Pro Tyr Asp Ala Ile Ile Ser Glu Glu Leu Leu Met Thr

65 70 75 80

Asp Pro Asn Tyr Arg Phe Lys Gln Ser Asp Val Ile Asn Glu Ile Leu

85 90 95

Asp Gly Tyr Val Ile Lys Val Asn Gly Asn Tyr Tyr Val Tyr Leu Lys

100 105 110

Pro Gly Ser Lys Arg Lys Asn Ile Arg Thr Lys Gln Gln Ile Ala Glu

115 120 125

Gln Val Ala Lys Gly Thr Lys Glu Ala Lys Glu Lys Gly Leu Ala Gln

130 135 140

Val Ala His Leu Ser Lys Glu Glu Val Ala Ala Val Asn Glu Ala Lys

145 150 155 160

Arg Gln Gly Arg Tyr Thr Thr Asp Asp Gly Tyr Ile Phe Ser Pro Thr

165 170 175

Asp Ile Ile Asp Asp Leu Gly Asp Ala Tyr Leu Val Pro His Gly Asn

180 185 190

His Tyr His Tyr Ile Pro Lys Lys Asp Leu Ser Pro Ser Glu Leu Ala

195 200 205

Ala Ala Gln Ala Tyr Trp Ser Gln Lys Gln Gly Arg Gly Ala Arg Pro

210 215 220

Ser Asp Tyr Arg Pro Thr Pro Ala Pro Gly Arg Arg Lys Ala Pro Ile

225 230 235 240

Pro Asp Val Thr Pro Asn Pro Gly Gln Gly His Gln Pro Asp Asn Gly

245 250 255

Gly Tyr His Pro Ala Pro Pro Arg Pro Asn Asp Ala Ser Gln Asn Lys

260 265 270

His Gln Arg Asp Glu Phe Lys Gly Lys Thr Phe Lys Glu Leu Leu Asp

275 280 285

Gln Leu His Arg Leu Asp Leu Lys Tyr Arg His Val Glu Glu Asp Gly

290 295 300

Leu Ile Phe Glu Pro Thr Gln Val Ile Lys Ser Asn Ala Phe Gly Tyr

305 310 315 320

Val Val Pro His Gly Asp His Tyr His Ile Ile Pro Arg Ser Gln Leu

325 330 335

Ser Pro Leu Glu Met Glu Leu Ala Asp Arg Tyr Leu Ala Gly Gln Thr

340 345 350

Glu Asp Asn Asp Ser Gly Ser Glu His Ser Lys Pro Ser Asp Lys Glu

355 360 365

Val Thr His Thr Phe Leu Gly His Arg Ile Lys Ala Tyr Gly Lys Gly

370 375 380

Leu Asp Gly Lys Pro Tyr Asp Thr Ser Asp Ala Tyr Val Phe Ser Lys

385 390 395 400

Glu Ser Ile His Ser Val Asp Lys Ser Gly Val Thr Ala Lys His Gly

405 410 415

Asp His Phe His Tyr Ile Gly Phe Gly Glu Leu Glu Gln Tyr Glu Leu

420 425 430

Asp Glu Val Ala Asn Trp Val Lys Ala Lys Gly Gln Ala Asp Glu Leu

435 440 445

Ala Ala Ala Leu Asp Gln Glu Gln Gly Lys Glu Lys Pro Leu Phe Asp

450 455 460

Thr Lys Lys Val Ser Arg Lys Val Thr Lys Asp Gly Lys Val Gly Tyr

465 470 475 480

Met Met Pro Lys Asp Gly Lys Asp Tyr Phe Tyr Ala Arg Asp Gln Leu

485 490 495

Asp Leu Thr Gln Ile Ala Phe Ala Glu Gln Glu Leu Met Leu Lys Asp

500 505 510

Lys Lys His Tyr Arg Tyr Asp Ile Val Asp Thr Gly Ile Glu Pro Arg

515 520 525

Leu Ala Val Asp Val Ser Ser Leu Pro Met His Ala Gly Asn Ala Thr

530 535 540

Tyr Asp Thr Gly Ser Ser Phe Val Ile Pro His Ile Asp His Ile His

545 550 555 560

Val Val Pro Tyr Ser Trp Leu Thr Arg Asp Gln Ile Ala Thr Val Lys

565 570 575

Tyr Val Met Gln His Pro Glu Val Arg Pro Asp Val Trp Ser Lys Pro

580 585 590

Gly His Glu Glu Ser Gly Ser Val Ile Pro Asn Val Thr Pro Leu Asp

595 600 605

Lys Arg Ala Gly Met Pro Asn Trp Gln Ile Ile His Ser Ala Glu Glu

610 615 620

Val Gln Lys Ala Leu Ala Glu Gly Arg Phe Ala Thr Pro Asp Gly Tyr

625 630 635 640

Ile Phe Asp Pro Arg Asp Val Leu Ala Lys Glu Thr Phe Val Trp Lys

645 650 655

Asp Gly Ser Phe Ser Ile Pro Arg Ala Asp Gly Ser Ser Leu Arg Thr

660 665 670

Ile Asn Lys Ser Asp Leu Ser Gln Ala Glu Trp Gln Gln Ala Gln Glu

675 680 685

Leu Leu Ala Lys Lys Asn Thr Gly Asp Ala Thr Asp Thr Asp Lys Pro

690 695 700

Lys Glu Lys Gln Gln Ala Asp Lys Ser Asn Glu Asn Gln Gln Pro Ser

705 710 715 720

Glu Ala Ser Lys Glu Glu Lys Glu Ser Asp Asp Phe Ile Asp Ser Leu

725 730 735

Pro Asp Tyr Gly Leu Asp Arg Ala Thr Leu Glu Asp His Ile Asn Gln

740 745 750

Leu Ala Gln Lys Ala Asn Ile Asp Pro Lys Tyr Leu Ile Phe Gln Pro

755 760 765

Glu Gly Val Gln Phe Tyr Asn Lys Asn Gly Glu Leu Val Thr Tyr Asp

770 775 780

Ile Lys Thr Leu Gln Gln Ile Asn Pro

785 790

<210>16

<211>715

<212>蛋白质

<213>链球菌

<400>16

Met Thr Asp Pro Asn Tyr Arg Phe Lys Gln Ser Asp Val Ile Asn Glu

1 5 10 15

Ile Leu Asp Gly Tyr Val Ile Lys Val Asn Gly Asn Tyr Tyr Val Tyr

20 25 30

Leu Lys Pro Gly Ser Lys Arg Lys Asn Ile Arg Thr Lys Gln Gln Ile

35 40 45

Ala Glu Gln Val Ala Lys Gly Thr Lys Glu Ala Lys Glu Lys Gly Leu

50 55 60

Ala Gln Val Ala His Leu Ser Lys Glu Glu Val Ala Ala Val Asn Glu

65 70 75 80

Ala Lys Arg Gln Gly Arg Tyr Thr Thr Asp Asp Gly Tyr Ile Phe Ser

85 90 95

Pro Thr Asp Ile Ile Asp Asp Leu Gly Asp Ala Tyr Leu Val Pro His

100 105 110

Gly Asn His Tyr His Tyr Ile Pro Lys Lys Asp Leu Ser Pro Ser Glu

115 120 125

Leu Ala Ala Ala Gln Ala Tyr Trp Ser Gln Lys Gln Gly Arg Gly Ala

130 135 140

Arg Pro Ser Asp Tyr Arg Pro Thr Pro Ala Pro Gly Arg Arg Lys Ala

145 150 155 160

Pro Ile Pro Asp Val Thr Pro Asn Pro Gly Gln Gly His Gln Pro Asp

165 170 175

Asn Gly Gly Tyr His Pro Ala Pro Pro Arg Pro Asn Asp Ala Ser Gln

180 185 190

Asn Lys His Gln Arg Asp Glu Phe Lys Gly Lys Thr Phe Lys Glu Leu

195 200 205

Leu Asp Gln Leu His Arg Leu Asp Leu Lys Tyr Arg His Val Glu Glu

210 215 220

Asp Gly Leu Ile Phe Glu Pro Thr Gln Val Ile Lys Ser Asn Ala Phe

225 230 235 240

Gly Tyr Val Val Pro His Gly Asp His Tyr His Ile Ile Pro Arg Ser

245 250 255

Gln Leu Ser Pro Leu Glu Met Glu Leu Ala Asp Arg Tyr Leu Ala Gly

260 265 270

Gln Thr Glu Asp Asn Asp Ser Gly Ser Glu His Ser Lys Pro Ser Asp

275 280 285

Lys Glu Val Thr His Thr Phe Leu Gly His Arg Ile Lys Ala Tyr Gly

290 295 300

Lys Gly Leu Asp Gly Lys Pro Tyr Asp Thr Ser Asp Ala Tyr Val Phe

305 310 315 320

Ser Lys Glu Ser Ile His Ser Val Asp Lys Ser Gly Val Thr Ala Lys

325 330 335

His Gly Asp His Phe His Tyr Ile Gly Phe Gly Glu Leu Glu Gln Tyr

340 345 350

Glu Leu Asp Glu Val Ala Asn Trp Val Lys Ala Lys Gly Gln Ala Asp

355 360 365

Glu Leu Ala Ala Ala Leu Asp Gln Glu Gln Gly Lys Glu Lys Pro Leu

370 375 380

Phe Asp Thr Lys Lys Val Ser Arg Lys Val Thr Lys Asp Gly Lys Val

385 390 395 400

Gly Tyr Met Met Pro Lys Asp Gly Lys Asp Tyr Phe Tyr Ala Arg Asp

405 410 415

Gln Leu Asp Leu Thr Gln Ile Ala Phe Ala Glu Gln Glu Leu Met Leu

420 425 430

Lys Asp Lys Lys His Tyr Arg Tyr Asp Ile Val Asp Thr Gly Ile Glu

435 440 445

Pro Arg Leu Ala Val Asp Val Ser Ser Leu Pro Met His Ala Gly Asn

450 455 460

Ala Thr Tyr Asp Thr Gly Ser Ser Phe Val Ile Pro His Ile Asp His

465 470 475 480

Ile His Val Val Pro Tyr Ser Trp Leu Thr Arg Asp Gln Ile Ala Thr

485 490 495

Val Lys Tyr Val Met Gln His Pro Glu Val Arg Pro Asp Val Trp Ser

500 505 510

Lys Pro Gly His Glu Glu Ser Gly Ser Val Ile Pro Asn Val Thr Pro

515 520 525

Leu Asp Lys Arg Ala Gly Met Pro Asn Trp Gln Ile Ile His Ser Ala

530 535 540

Glu Glu Val Gln Lys Ala Leu Ala Glu Gly Arg Phe Ala Thr Pro Asp

545 550 555 560

Gly Tyr Ile Phe Asp Pro Arg Asp Val Leu Ala Lys Glu Thr Phe Val

565 570 575

Trp Lys Asp Gly Ser Phe Ser Ile Pro Arg Ala Asp Gly Ser Ser Leu

580 585 590

Arg Thr Ile Asn Lys Ser Asp Leu Ser Gln Ala Glu Trp Gln Gln Ala

595 600 605

Gln Glu Leu Leu Ala Lys Lys Asn Thr Gly Asp Ala Thr Asp Thr Asp

610 615 620

Lys Pro Lys Glu Lys Gln Gln Ala Asp Lys Ser Asn Glu Asn Gln Gln

625 630 635 640

Pro Ser Glu Ala Ser Lys Glu Glu Lys Glu Ser Asp Asp Phe Ile Asp

645 650 655

Ser Leu Pro Asp Tyr Gly Leu Asp Arg Ala Thr Leu Glu Asp His Ile

660 665 670

Asn Gln Leu Ala Gln Lys Ala Asn Ile Asp Pro Lys Tyr Leu Ile Phe

675 680 685

Gln Pro Glu Gly Val Gln Phe Tyr Asn Lys Asn Gly Glu Leu Val Thr

690 695 700

Tyr Asp Ile Lys Thr Leu Gln Gln Ile Asn Pro

705 710 715

<210>17

<211>77

<212>蛋白质

<213>链球菌

<400>17

Met His Ser Phe Ser Asn Pro Gly Tyr Pro Tyr Asp Asn Ala Val Thr

1 5 10 15

Glu Ala Phe Phe Lys Tyr Leu Lys His Arg Gln Ile Asn Arg Lys His

20 25 30

Tyr Gln Asn Ile Lys Gln Val Gln Leu Asp Cys Phe Glu Tyr Ile Glu

35 40 45

Asn Phe Tyr Asn Asn Tyr Asn Pro His Thr Ala Asn Leu Gly Leu Thr

50 55 60

Pro Asn Gln Lys Glu Glu Asn Tyr Phe Aan Ala Ile Lys

65 70 75

<210>18

<211>86

<212>蛋白质

<213>链球菌

<400>16

Met Ala Tyr Tyr Gln Ala Cys Thr Glu Lys Asp Ile Ile Arg Ser Met

1 5 10 15

Ser Arg Lys Gly Thr Pro Ala Asp Asn Ala Cys Ile Glu Trp Phe His

20 25 30

Thr Val Leu Lys Thr Glu Thr Phe Tyr Phe His Asn Arg Arg Lys Tyr

35 40 45

Asn Lys Asp Ser Ile Thr Asn Ile Val Lys Asn Tyr Ile Thr Phe Tyr

50 55 60

Asn Glu Thr Arg Ile Gln Gln Arg Leu Asn Asp Gln Ser Pro Val Gln

65 70 75 80

Tyr Arg Lys Leu Ile Ala

85

<210>19

<211>126

<212>蛋白质

<213>链球菌

<400>19

Met Glu Asn His Phe Ile Tyr Gly Tyr Arg Thr Ile Thr Arg Leu Leu

1 5 10 15

Lys Lys Ile His Gly Leu Thr Val Asn Thr Lys Lys Val Tyr Arg Ile

20 25 30

Met Lys Asn Asn Gly Trp Leu Cys Arg Thr Arg Thr Lys Lys Val Pro

35 40 45

Asn Leu Gly Lys Ala Tyr Tyr Leu Thr Asp Asn Lys Leu Ser Arg Asp

50 55 60

Phe His Ala Asp Lys Pro Lys Glu Lys Leu Val Thr Asp Ile Thr Tyr

65 70 75 80

Leu Tyr Phe Gly Asn Cys Lys Leu Tyr Leu Ser Ser Ile Met Asn Leu

85 90 95

Tyr Asn Arg Glu Ile Ile Ala Tyr Thr Ile Ser Asp Cys Gln Asp Thr

100 105 110

Asp Phe Val Leu Asp Thr Leu Asn Gln Leu Lys Leu Pro Lys

115 120 125

<210>20

<211>96

<212>蛋白质

<213>链球菌

<400>20

Met Val Lys Lys Ala Tyr Ser Trp Glu Thr Lys Leu Ala Cys Ile Asp

1 5 10 15

Met Lys Lys Ala Gly Lys Ser Asn Arg Val Ile Met Glu Thr Leu Gly

20 25 30

Ile Lys Asn Asn Ser Gln Ile Tyr Thr Trp Met Lys Trp Tyr Glu Asn

35 40 45

Glu Glu Leu Tyr Arg Phe His Gln Gly Val Gly Lys Gln Tyr Thr Tyr

50 55 60

Gly Lys Gly Leu Glu His Leu Ser Glu Val Glu Gln Leu Gln Leu Gln

65 70 75 80

Val Asp Leu Leu Lys Lys Tyr Arg Gly Leu Ile Arg Lys Ser Ile Lys

85 90 95

<210>21

<211>288

<212>蛋白质

<213>链球菌

<400>21

Ile Arg Tyr Pro Lys Ala Ser Ser Gly Asp Tyr Gly Thr Lys Arg Glu

1 5 10 15

Ile Ile Thr Ala Asn Lys Asp Lys Tyr Ser Ile Ser Lys Met Cys Arg

20 25 30

Trp Leu Asn Met Pro His Ser Ser Tyr Tyr Tyr Gln Ala Val Glu Ser

35 40 45

Val Ser Glu Thr Glu Phe Glu Glu Thr Ile Lys Arg Ile Phe Leu Asp

50 55 60

Ser Glu Ser Arg Tyr Gly Ser Arg Lys Ile Lys Ile Cys Leu Asn Asn

65 70 75 80

Glu Gly Ile Thr Leu Ser Arg Arg Arg Ile Arg Arg Ile Met Lys Arg

85 90 95

Leu Asn Leu Val Ser Val Tyr Gln Lys Ala Thr Phe Lys Pro His Ser

100 105 110

Arg Gly Lys Asn GLu Ala Pro Ile Pro Asn His Leu Asp Arg Gln Phe

115 120 125

Lys Gln Glu Arg Pro Leu Gln Ala Leu Val Thr Asp Leu Thr Tyr Val

130 135 140

Arg Val Gly Asn Arg Trp Ala Tyr Val Cys Leu Ile Ile Asp Leu Tyr

145 150 155 160

Asn Arg Glu Ile Ile Gly Leu Ser Leu Gly Trp His Lys Thr Ala Glu

165 170 175

Leu Val Lys Gln Ala Ile Gln Ser Ile Pro Tyr Ala Leu Thr Lys Val

180 185 190

Lys Met Phe His Ser Asp Arg Gly Lys Glu Phe Asp Asn Gln Leu Ile

195 200 205

Asp Glu Ile Leu Glu Ala Phe Gly Ile Thr Arg Ser Leu Ser Gln Ala

210 215 220

Gly Tyr Pro Tyr Asp Asn Ala Val Ala Glu Ser Thr Tyr Arg Ala Phe

225 230 235 240

Lys Ile Glu Phe Val Tyr Gln Glu Thr Phe Gln Leu Leu Glu Glu Leu

245 250 255

Ala Leu Lys Thr Lys Asp Tyr Val His Trp Trp Asn Tyr His Arg Ile

260 265 270

His Gly Ser Leu Asn Tyr Gln Thr Pro Met Thr Lys Arg Leu Ile Ala

275 280 285

<210>22

<211>5058

<212>DNA

<213>链球菌

<220>

<221>CDS

<222>(1)...(663)

<221>CDS

<222>(763)...(1344)

<221>CDS

<222>(1362)...(1739)

<221>CDS

<222>(2266)...(5058)

<400>22

aat ttg aaa gca gaa tta tct gta gaa gat gag caa tat aca gca aca 48

Asn Leu Lys Ala Glu Leu Ser Val Glu Asp Glu Gln Tyr Thr Ala Thr

1 5 10 15

gtt tat ggt aaa tct gct cat ggt tca aca cca caa gaa ggt gtt aat 96

Val Tyr Gly Lys Ser Ala His Gly Ser Thr Pro Gln Glu Gly Val Asn

20 25 30

ggg gcg act tat tta gct ctt tat cta agt caa ttt gat ttt gaa ggt 144

Gly Ala Thr Tyr Leu Ala Leu Tyr Leu Ser Gln Phe Asp Phe Glu Gly

35 40 45

cct gct cgt gct ttc tta gat gtt aca gcc aac att att cac gaa gac 192

Pro Ala Arg Ala Phe Leu Asp Val Thr Ala Asn Ile Ile His Glu Asp

50 55 60

ttc tca ggt gaa aaa ctt gga gta gct tat gaa gat gac tgt atg gga 240

Phe Ser Gly Glu Lys Leu Gly Val Ala Tyr Glu Asp Asp Cys Met Gly

65 70 75 80

cca ttg agc atg aat gca ggt gtc ttc cag ttt gat gaa act aat gat 288

Pro Leu Ser Met Asn Ala Gly Val Phe Gln Phe Asp Glu Thr Asn Asp

85 90 95

gat aat act atc gct ctt aat ttc cgt tac cca caa ggg aca gat gct 336

Asp Asn Thr Ile Ala Leu Asn Phe Arg Tyr Pro Gln Gly Thr Asp Ala

100 105 110

aaa act atc caa act aag ctt gag aaa ctt aac gga gtt gaa aaa gtg 384

Lys Thr Ile Gln Thr Lys Leu Glu Lys Leu Asn Gly Val Glu Lys Val

115 120 125

act ctt tct gac cat gaa cac aca cca cac tat gta cct atg gac gat 432

Thr Leu Ser Asp His Glu His Thr Pro His Tyr Val Pro Met Asp Asp

130 135 140

gaa tta gta tca acc tta cta gct gtc tat gaa aag caa act ggt ctt 480

Glu Leu Val Ser Thr Leu Leu Ala Val Tyr Glu Lys Gln Thr Gly Leu

145 150 155 160

aaa gga cat gaa cag gtt att ggt ggt ggg aca ttt ggt cgc tta ctt 528

Lys Gly His Glu Gln Val Ile Gly Gly Gly Thr Phe Gly Arg Leu Leu

165 170 175

gaa cgg ggt gtt gca tac ggt gcc atg ttc cca gga gat gaa aac act 576

Glu Arg Gly Val Ala Tyr Gly Ala Met Phe Pro Gly Asp Glu Asn Thr

180 185 190

atg cat caa gct aat gag tac atg cct tta gaa aat att ttc cgt tcg 624

Met His Gln Ala Asn Glu Tyr Met Pro Leu Glu Asn Ile Phe Arg Ser

195 200 205

gct gct atc tac gca gaa gct atc tat gaa tta atc aaa taaaataatc 673

Ala Ala Ile Tyr Ala Glu Ala Ile Tyr Glu Leu Ile Lys

210 215 220

cttaaactaa atatgtgatc aatgataaag ggtggtgaag acatgaaagt gtctttgcct 733

cttttcataa ggttagattt ggagacttt atg act gac ttg gaa aaa att att 786

Met Thr Asp Leu Glu Lys Ile Ile

225

aaa gca ata aaa agt gat tca cag aat caa aat tat aca gaa aat ggt 834

Lys Ala Ile Lys Ser Asp Ser Gln Asn Gln Asn Tyr Thr Glu Asn Gly

230 235 240 245

att gat cct ttg ttt gct gct cct aaa aca gct agg atc aat att gtt 882

Ile Asp Pro Leu Phe Ala Ala Pro Lys Thr Ala Arg Ile Asn Ile Val

250 255 260

ggc caa gca cct ggt tta aaa act caa gaa gca aga ctc tat tgg aaa 930

Gly Gln Ala Pro Gly Leu Lys Thr Gln Glu Ala Arg Leu Tyr Trp Lys

265 270 275

gat aaa tct gga gat cgt cta cgc cag tgg ctt gga gtt gat gaa gag 978

Asp Lys Ser Gly Asp Arg Leu Arg Gln Trp Leu Gly Val Asp Glu Glu

280 285 290

aca ttt tac cat tct gga aaa ttt gct gtt tta cct tta gat ttt tat 1026

Thr Phe Tyr His Ser Gly Lys Phe Ala Val Leu Pro Leu Asp Phe Tyr

295 300 305

tac cca ggc aaa gga aaa tca gga gat tta ccc cct aga aaa ggt ttt 1074

Tyr Pro Gly Lys Gly Lys Ser Gly Asp Leu Pro Pro Arg Lys Gly Phe

310 315 320 325

gcg gag aaa tgg cac cct ctt att tta aaa gaa atg cct aat gtt caa 1122

Ala Glu Lys Trp His Pro Leu Ile Leu Lys Glu Met Pro Asn Val Gln

330 335 340

ttg acc ttg cta gtt ggt cag tat gct cag aaa tat tat ctt gga agc 1170

Leu Thr Leu Leu Val Gly Gln Tyr Ala Gln Lys Tyr Tyr Leu Gly Ser

345 350 355

tcc gca cat aaa aat cta aca gaa aca gtt aaa gct tac aaa gac tat 1218

Ser Ala His Lys Asn Leu Thr Glu Thr Val Lys Ala Tyr Lys Asp Tyr

360 365 370

cta ccc gat tat tta ccc ctg gtt cac cca tca ccg cga aat caa att 1266

Leu Pro A5p Tyr Leu Pro Leu Val His Pro Ser Pro Arg Asn Gln Ile

375 380 385

tgg cta aag aag aat cca tgg ttt gaa aaa gat cta atc gtt gat tta 1314

Trp Leu Lys Lys Asn Pro Trp Phe Glu Lys Asp Leu Ile Val Asp Leu

390 395 400 405

caa aag ata gta gca gat att tta aaa gat taaggatagg agttggt atg 1364

Gln Lys Ile Val Ala Asp Ile Leu Lys Asp Met

410 415

aga gat aat cat cta cac acg tat ttt tcc tat gat tgt caa acg gca 1412

Arg Asp Asn His Leu His Thr Tyr Phe Ser Tyr Asp Cys Gln Thr Ala

420 425 430

ttt gag gac tat atc aat ggt ttt aca ggt gaa ttt atc acg aca gaa 1460

Phe Glu Asp Tyr Ile Asn Gly Phe Thr Gly Glu Phe Ile Thr Thr Glu

435 440 445

cat ttt gat tta tca aat cct tac acc ggt caa gac gat gtt cct gat 1508

His Phe Asp Leu Ser Asn Pro Tyr Thr Gly Gln Asp Asp Val Pro Asp

450 455 460

tat agt gct tat tgt caa aaa ata gat tat ctt aat cag aaa tat gga 1556

Tyr Ser Ala Tyr Cys GLn Lys Ile Asp Tyr Leu Asn Gln Lys Tyr Gly

465 470 475 480

aat cga ttt aaa aaa gga att gaa atc ggt tat ttt aaa gat agg gaa 1604

Asn Arg Phe Lys Lys Gly Ile Glu Ile Gly Tyr Phe Lys Asp Arg Glu

485 490 495

tca gat att tta gat tat tta aaa aat aaa gaa ttt gat tta aaa cta 1652

Ser Asp Ile Leu Asp Tyr Leu Lys Asn Lys Glu Phe Asp Leu Lys Leu

500 505 510

ttg tca atc cat cat aat ggt agg tat gat tat ctg caa gaa gaa gct 1700

Leu Ser Ile His His Asn Gly Arg Tyr Asp Tyr Leu Gln Glu Glu Ala

515 520 525

ctg aaa gta cca aca aag gga gct ttt agc aga tra ctt taatcgtatg 1749

Leu Lys Val Pro Thr Lys Gly Ala Phe Ser Arg Leu Leu

530 535 540

gaatttgcca taggccgtgt ggaagcgcac gttttagctc actttgatta tggttttcgt 1809

aagttaaact tagatgtaga agatttaaaa ccgtttgaaa cgcaattgaa gcgcattttc 1869

ataaagatgt tatctaaggg gttagctttt gaactaaata ccaaatccct ttatctatat 1929

gggaatgaaa aactttatcg ctatgcttta gagatactca aacagcttgg ttgtaaacaa 1989

tactctatag gctctgacgg tcatattcct gaacattttt gttatgaatt tgatagactt 2049

caaggtctgc taaaggacta tcaaattgat gaaaatcatt tgatatgagg aaatttttga 2109

taaaaaagct aggcaatatt gcttagcttt tttgtaatgc tattgatagt tttagtgaaa 2169

atttcaaaaa aataaagaaa tcatttactt gttgcaagcg cttgcgtaaa ttgttatgat 2229

tttattggta acaattcatt aaaaaaggag aatgat atg aaa aga aaa gac tta 2283

Met Lys Arg Lys Asp Leu

545

ttt ggt gat aaa caa act caa tac acg att aga aag tta agt gtt gga 2331

Phe Gly Asp Lys Gln Thr Gln Tyr Thr Ile Arg Lys Leu Ser Val Gly

550 555 560

gta gct tca gtt aca aca ggg gta tgt att ttt ctt cat agt cca cag 2379

Val Ala Ser Val Thr Thr Gly Val Cys Ile Phe Leu His Ser Pro Gln

565 570 575

gta ttt gct gaa gaa gta agt gtt tct cct gca act aca gcg att gca 2427

Val Phe Ala Glu Glu Val Ser Val Ser Pro Ala Thr Thr Ala Ile Ala

580 585 590 595

gag tcg aat att aat cag gtt gac aac caa caa tct act aat tta aaa 2475

Glu Ser Asn Ile Asn Gln Val Asp Asn Gln Gln Ser Thr Asn Leu Lys

600 605 610

gat gac ata aac tca aac tct gag acg gtt gtg aca ccc tca gat atg 2523

Asp Asp Ile Asn Ser Asn Ser Glu Thr Val Val Thr Pro Ser Asp Met

615 620 625

ccg gat acc aag caa tta gta tca gat gaa act gac act caa aag gga 2571

Pro Asp Thr Lys Gln Leu Val Ser Asp Glu Thr Asp Thr Gln Lys Gly

630 635 640

gtg aca gag ccg gat aag gcg aca agc ctg ctt gaa gaa aat aaa ggt 2619

Val Thr Glu Pro Asp Lys Ala Thr Ser Leu Leu Glu Glu Asn Lys Gly

645 650 655

cct gtt tca gat aaa aat acc tta gat tta aaa gta gca cca tct aca 2667

Pro Val Ser Asp Lys Asn Thr Leu Asp Leu Lys Val Ala Pro Ser Thr

660 665 670 675

ttg caa aat act ccc gac aaa act tct caa gct ata ggt gct cca agc 2715

Leu Gln Asn Thr Pro Asp Lys Thr Ser Gln Ala Ile Gly Ala Pro Ser

680 685 690

cct acc ttg aaa gta gct aat caa gct cca cgg att gaa aat ggt tac 2763

Pro Thr Leu Lys Val Ala Asn Gln Ala Pro Arg Ile Glu Asn Gly Tyr

695 700 705

ttt agg cta cat ctt aaa gaa ttg cct caa ggt cat cct gta gaa agc 2811

Phe Arg Leu His Leu Lys Glu Leu Pro Gln Gly His Pro Val Glu Ser

710 715 720

act gga ctt tgg ata tgg gga gat gtt gat caa ccg tct agt aat tgg 2859

Thr Gly Leu Trp Ile Trp Gly Asp Val Asp Gln Pro Ser Ser Asn Trp

725 730 735

cca aat ggt gct atc cct atg act gat gct aag aaa gat gat tac ggt 2907

Pro Asn Gly Ala Ile Pro Met Thr Asp Ala Lys Lys Asp Asp Tyr Gly

740 745 750 755

tat tat gtt gat ttt aaa tta tct gaa aaa caa cga aaa caa ata tct 2955

Tyr Tyr Val Asp Phe Lys Leu Ser Glu Lys Gln Arg Lys Gln Ile Ser

760 765 770

ttt tta att aat aac aaa gca ggg aca aat tta agc ggc gat cat cat 3003

Phe Leu Ile Asn Asn Lys Ala Gly Thr Asn Leu Ser Gly Asp His His

775 780 785

att cca tta tta cga cct gag atg aac caa gtt tgg att gat gaa aag 3051

Ile Pro Leu Leu Arg Pro Glu Met Asn Gln Val Trp Ile Asp Glu Lys

790 795 800

tac ggt ata cat act tat caa ccc ctc aaa gaa ggg tat gtc cgt att 3099

Tyr Gly Ile His Thr Tyr Gln Pro Leu Lys Glu Gly Tyr Val Arg Ile

805 810 815

aac tat ttg agt tcc tct agt aac tat gac cac tta tca gca tgg ctc 3147

Asn Tyr Leu Ser Ser Ser Ser Asn Tyr Asp His Leu Ser Ala Trp Leu

820 825 830 835

ttt aaa gat gtt gca acc ccy tca aca act tgg cca gat ggt agt aat 3195

Phe Lys Asp Val Ala Thr Xaa Ser Thr Thr Trp Pro Asp Gly Ser Asn

840 845 850

ttt gtg aat caa gga cta tat gga agg tat att gat gta tca cta aaa 3243

Phe Val Asn Gln Gly Leu Tyr Gly Arg Tyr Ile Asp Val Ser Leu Lys

855 860 865

act aac gcc aaa gag att ggt ttt cta atc tta gat gaa agt aag aca 3291

Thr Asn Ala Lys Glu Ile Gly Phe Leu Ile Leu Asp Glu Ser Lys Thr

870 875 880

gga gat gca gtg aaa gtt caa ccc aac gac tat gtt ttt aga gat tta 3339

Gly Asp Ala Val Lys Val Gln Pro Asn Asp Tyr Val Phe Arg Asp Leu

885 890 895

gct aac cat aac caa att ttt gta aaa gat aag gat cca aag gtt tat 3387

Ala Asn His Asn Gln Ile Phe Val Lys Asp Lys Asp Pro Lys Val Tyr

900 905 910 915

aat aat cct tat tac att gat caa gtg cag cta aag gat gcc caa caa 3435

Asn Asn Pro Tyr Tyr Ile Asp Gln Val Gln Leu Lys Asp Ala Gln Gln

920 925 930

att gat tta aca agt att caa gca agt ttt aca act cta gat ggg gta 3483

Ile Asp Leu Thr Ser Ile Gln Ala Ser Phe Thr Thr Leu Asp Gly Val

935 940 945

gat aaa act gaa att tta aaa gaa ttg aaa gtg act gat aaa aat caa 3531

Asp Lys Thr Glu Ile Leu Lys Glu Leu Lys Val Thr Asp Lys Asn Gln

950 955 960

aat gct ata caa att tct gat atc act ctc gat act agt aaa tct ctt 3579

Asn Ala Ile Gln Ile Ser Asp Ile Thr Leu Asp Thr Ser Lys Ser Leu

965 970 975

tta ata atc aaa ggc gac ttt aat cct aaa caa ggt cat ttc aac ata 3627

Leu Ile Ile Lys Gly Asp Phe Asn Pro Lys Gln Gly His Phe Asn Ile

980 985 990 995

tct tat aat ggt aac aat gtc atg aca agg caa tct tgg gaa ttt aaa 3675

Ser Tyr Asn Gly Asn Asn Val Met Thr Arg Gln Ser Trp Glu Phe Lys

1000 1005 1010

gac caa ctt tat gct tat agt gga aat tta ggt gca gtt ctc aat caa 3723

Asp Gln Leu Tyr Ala Tyr Ser Gly Asn Leu Gly Ala Val Leu Asn Gln

1015 1020 1025

gat ggt tta aaa gtt gaa gcc agc ctc tgg tca ccg agt gct gat agt 3771

Asp Gly Ser Lys Val Glu Ala Ser Leu Trp Ser Pro Ser Ala Asp Ser

1030 1035 1040

gtc act atg att att tat gac aaa gat aac caa aac agg gtt gta gcg 3819

Val Thr Met Ile Ile Tyr Asp Lys Asp Asn Gln Asn Arg Val Val Ala

1045 1050 1055

act acc ccc ctt gtg aaa aat aat aaa ggt gtt tgg cag acg ata ctt 3867

Thr Thr Pro Leu Val Lys Asn Asn Lys Gly Val Trp Gln Thr Ile Leu

1060 1065 1070 1075

gat act aaa tta ggt att aaa aac tat act ggt tac tat tat ctt tac 3915

Asp Thr Lys Leu Gly Ile Lys Asn Tyr Thr Gly Tyr Tyr Tyr Leu Tyr

1080 1085 1090

gaa ata aaa aga ggt aag gat aag gtt aag att tta gat cct tat gca 3963

Glu Ile Lys Arg Gly Lys Asp Lys Val Lys Ile Leu Asp Pro Tyr Ala

1095 1100 1105

aag tca tta gca gag tgg gat agt aat act gtt aat gat gat att aaa 4011

Lys Ser Leu Ala Glu Trp Asp Ser Asn Thr Val Asn Asp Asp Ile Lys

1110 1115 1120

acg gct aaa gca gct ttt gta aat cca agt caa ctt gga cct caa aat 4059

Thr Ala Lys Ala Ala Phe Val Asn Pro Ser Gln Leu Gly Pro Gln Asn

1125 1130 1135

tta agt ttt gct aaa att gct aat ttt aaa gga aga caa gat gct gtt 4107

Leu Ser Phe Ala Lys Ile Ala Asn Phe Lys Gly Arg Gln Asp Ala Val

1140 1145 1150 1155

ata tac gaa gca cat gta aga gac ttc act tct gat cga tct ttg gat 4155

Ile Tyr Glu Ala His Val Arg Asp Phe Thr Ser Asp Arg Ser Leu Asp

1160 1165 1170

gga aaa tta aaa aat caa ttt ggt acc ttt gca gcc ttt tca gag aaa 4203

Gly Lys Leu Lys Asn Gln Phe Gly Thr Phe Ala Ala Phe Ser Glu Lys

1175 1180 1185

cta gat tat tta cag aaa tta gga gtt aca cac att cag ctt tta ccg 4251

Leu Asp Tyr Leu Gln Lys Leu Gly Val Thr His Ile Gln Leu Leu Pro

1190 1195 1200

gta ttg agt tat ttt tat gtt aat gaa atg gat aag tca cgc tca aca 4299

Val Leu Ser Tyr Phe Tyr Val Asn Glu Met Asp Lys Ser Arg Ser Thr

1205 1210 1215

gct tac act tcc tca gac aat aat tac aat tgg ggc tat gac cca cag 4347

Ala Tyr Thr Ser Ser Asp Asn Asn Tyr Asn Trp Gly Tyr Asp Pro Gln

1220 1225 1230 1235

agc tat ttt gct ctt tct ggg atg tat tca gag aaa cca aaa gat cca 4395

Ser Tyr Phe Ala Leu Ser Gly Met Tyr Ser Glu Lys Pro Lys Asp Pro

1240 1245 1250

tca gca cgt atc gcc gaa tta aaa caa tta ata cat gat att cat aaa 4443

Ser Ala Arg Ile Ala Glu Leu Lys Gln Leu Ile His Asp Ile His Lys

1255 1260 1265

cgt ggc acg ggg gtt ata ctt gat gtc gtc tat aat cac act gca aaa 4491

Arg Gly Met Gly Val Ile Leu Asp Val Val Tyr Asn His Thr Ala Lys

1270 1275 1280

act tat ctc ttt gag gat ata gaa cct aat tat tat cac ttt atg aat 4539

Thr Tyr Leu Phe Glu Asp Ile Glu Pro Asn Tyr Tyr His Phe Met Asn

1285 1290 1295

gaa gat ggt tca cca aga gaa agt ttt gga ggg gga cgt tta gga acc 4587

Glu Asp Gly Ser Pro Arg Glu Ser Phe Gly Gly Gly Arg Leu Gly Thr

1300 1305 1310 1315

act cat gca atg agt cgt cgt gtt ttg gtt gat tcc att aaa tat ctt 4635

Thr His Ala Met Ser Arg Arg Val Leu Val Asp Ser Ile Lys Tyr Leu

1320 1325 1330

aca agt gaa ttt aaa gtt gat ggt ttc cgt ttt gat atg atg gga gat 4683

Thr Ser Glu Phe Lys Val Asp Gly Phe Arg Phe Asp Met Met Gly Asp

1335 1340 1345

cat gat gcg gct gcg att gaa tta gct tat aaa gaa gct aaa gct att 4731

His Asp Ala Ala Ala Ile Glu Leu Ala Tyr Lys Glu Ala Lys Ala Ile

1350 1355 1360

aat cct aat atg att atg att ggt gag ggc tgg aga aca ttc caa ggc 4779

Asn Pro Asn Met Ile Met Ile Gly Glu Gly Trp Arg Thr Phe Gln Gly

1365 1370 1375

gat caa ggt cag ccg gtt aaa cca gct gac caa gat tgg atg aag tca 4827

Asp Gln Gly Gln Pro Val Lys Pro Ala Asp Gln Asp Trp Met Lys Ser

1380 1385 1390 1395

acc gat aca gtt ggc gtc ttt tca gat gat att cgt aat agc ttg aaa 4875

Thr Asp Thr Val Gly Val Phe Ser Asp Asp Ile Arg Asn Ser Leu Lys

1400 1405 1410

tct ggt ttt cca aat gaa ggt act cca gct ttc atc aca ggt ggc cca 4923

Ser Gly Phe Pro Asn Glu Gly Thr Pro Ala Phe Ile Thr Gly Gly Pro

1415 1420 1425

caa tct tta caa ggt att ttt aaa aat atc aaa gca caa cct ggg aat 4971

Gln Ser Leu Gln Gly Ile Phe Lys Asn Ile Lys Ala Gln Pro Gly Asn

1430 1435 1440

ttt gaa gca gat tcg cca gga gat gtg gtg cag tat att gct gca cat 5019

Phe Glu Ala Asp Ser Pro Gly Asp Val Val Gln Tyr Ile Ala Ala His

1445 1450 1455

gat aac ctt acc ttg cat gat gtg att gca aaa tca att 5058

Asp Asn Leu Thr Leu His Asp Val Ile Ala Lys Ser Ile

1460 1465 1470

<210>23

<211>221

<212>蛋白质

<213>链球菌

<400>23

Asn Leu Lys Ala Glu Leu Ser Val Glu Asp Glu Gln Tyr Thr Ala Thr

1 5 10 15

Val Tyr Gly Lys Ser Ala His Gly Ser Thr Pro Gln Glu Gly Val Asn

20 25 30

Gly Ala Thr Tyr Leu Ala Leu Tyr Leu Ser Gln Phe Asp Phe Glu Gly

35 40 45

Pro Ala Arg Ala Phe Leu Asp Val Thr Ala Asn Ile Ile His Glu Asp

50 55 60

Phe Ser Gly Glu Lys Leu Gly Val Ala Tyr Glu Asp Asp Cys Met Gly

65 70 75 80

Pro Leu Ser Met Asn Ala Gly Val Phe Gln Phe Asp Glu Thr Asn Asp

85 90 95

Asp Asn Thr Ile Ala Leu Asn Phe Arg Tyr Pro Gln Gly Thr Asp Ala

100 105 110

Lys Thr Ile Gln Thr Lys Leu Glu Lys Leu Asn Gly Val Glu Lys Val

115 120 125

Thr Leu Ser Asp His Glu His Thr Pro His Tyr Val Pro Met Asp Asp

130 135 140

Glu Leu Val Ser Thr Leu Leu Ala Val Tyr Glu Lys Gln Thr Gly Leu

145 150 155 160

Lys Gly His Glu Gln Val Ile Gly Gly Gly Thr Phe Gly Arg Leu Leu

165 170 175

Glu Arg Gly Val Ala Tyr Gly Ala Met Phe Pro Gly Asp Glu Asn Thr

180 185 190

Met His Gln Ala Asn Glu Tyr Met Pro Leu Glu Asn Ile Phe Arg Ser

195 200 205

Ala Ala Ile Tyr Ala Glu Ala Ile Tyr Glu Leu Ile Lys

210 215 220

<210>24

<211>194

<212>蛋白质

<213>链球菌

<400>24

Met Thr Asp Leu Glu Lys Ile Ile Lys Ala Ile Lys Ser Asp Ser Gln

1 5 10 15

Asn Gln Asn Tyr Thr Glu Asn Gly Ile Asp Pro Leu Phe Ala Ala Pro

20 25 30

Lys Thr Ala Arg Ile Asn Ile Val Gly Gln Ala Pro Gly Leu Lys Thr

35 40 45

Gln Glu Ala Arg Leu Tyr Trp Lys Asp Lys Ser Gly Asp Arg Leu Arg

50 55 60

Gln Trp Leu Gly Val Asp Glu Glu Thr Phe Tyr His Ser Gly Lys Phe

65 70 75 80

Ala Val Leu Pro Leu Asp Phe Tyr Tyr Pro Gly Lys Gly Lys Ser Gly

85 90 95

Asp Leu Pro Pro Arg Lys Gly Phe Ala Glu Lys Trp His Pro Leu Ile

100 105 110

Leu Lys Glu Met Pro Asn Val Gln Leu Thr Leu Leu Val Gly Gln Tyr

115 120 125

Ala Gln Lys Tyr Tyr Leu Gly Ser Ser Ala His Lys Asn Leu Thr Glu

130 135 140

Thr Val Lys Ala Tyr Lys Asp Tyr Leu Pro Asp Tyr Leu Pro Leu Val

145 150 155 160

His Pro Ser Pro Arg Asn Gln Ile Trp Leu Lys Lys Asn Pro Trp Phe

165 170 175

Glu Lys Asp Leu Ile Val Asp Leu Gln Lys Ile Val Ala Asp Ile Leu

180 185 190

Lys Asp

<210>25

<211>126

<212>蛋白质

<213>链球菌

<400>25

Met Arg Asp Asn His Leu His Thr Tyr Phe Ser Tyr Asp Cys Gln Thr

1 5 10 15

Ala Phe Glu Asp Tyr Ile Asn Gly Phe Thr Gly Glu Phe Ile Thr Thr

20 25 30

Glu His Phe Asp Leu Ser Asn Pro Tyr Thr Gly Gln Asp Asp Val Pro

35 40 45

Asp Tyr Ser Ala Tyr Cys Gln Lys Ile Asp Tyr Leu Asn Gln Lys Tyr

50 55 60

Gly Asn Arg Phe Lys Lys Gly Ile Glu Ile Gly Tyr Phe Lys Asp Arg

65 70 75 80

Glu Ser Asp Ile Leu Asp Tyr Leu Lys Asn Lys Glu Phe Asp Leu Lys

85 90 95

Leu Leu Ser Ile His His Asn Gly Arg Tyr Asp Tyr Leu Gln Glu Glu

100 105 110

Ala Leu Lys Val Pro Thr Lys Gly Ala Phe Ser Arg Leu Leu

115 120 125

<210>26

<211>931

<212>蛋白质

<213>链球菌

<400>26

Met Lys Arg Lys Asp Leu Phe Gly Asp Lys Gln Thr Gln Tyr Thr Ile

1 5 10 15

Arg Lys Leu Ser Val Gly Val Ala Ser Val Thr Thr Gly Val Cys Ile

20 25 30

Phe Leu His Ser Pro Gln Val Phe Ala Glu Glu Val Ser Val Ser Pro

35 40 45

Ala Thr Thr Ala Ile Ala Glu Ser Asn Ile Asn Gln Val Asp Asn Gln

50 55 60

Gln Ser Thr Asn Leu Lys Asp Asp Ile Asn Ser Asn Ser Glu Thr Val

65 70 75 80

Val Thr Pro Ser Asp Met Pro Asp Thr Lys Gln Leu Val Ser Asp Glu

85 90 95

Thr Asp Thr Gln Lys Gly Val Thr Glu Pro Asp Lys Ala Thr Ser Leu

100 105 110

Leu Glu Glu Asn Lys Gly Pro Val Ser Asp Lys Asn Thr Leu Asp Leu

115 120 125

Lys Val Ala Pro Ser Thr Leu Gln Asn Thr Pro Asp Lys Thr Ser Gln

130 135 140

Ala Ile Gly Ala Pro Ser Pro Thr Leu Lys Val Ala Asn Gln Ala Pro

145 150 155 160

Arg Ile Glu Asn Gly Tyr Phe Arg Leu His Leu Lys Glu Leu Pro Gln

165 170 175

Gly His Pro Val Glu Ser Thr Gly Leu Trp Ile Trp Gly Asp Val Asp

180 185 190

Gln Pro Ser Ser Asn Trp Pro Asn Gly Ala Ile Pro Met Thr Asp Ala

195 200 205

Lys Lys Asp Asp Tyr Gly Tyr Tyr Val Asp Phe Lys Leu Ser Glu Lys

210 215 220

Gln Arg Lys Gln Ile Ser Phe Leu Ile Asn Asn Lys Ala Gly Thr Asn

225 230 235 240

Leu Ser Gly Asp His His Ile Pro Leu Leu Arg Pro Glu Met Asn Gln

245 250 255

Val Trp Ile Asp Glu Lys Tyr Gly Ile His Thr Tyr Gln Pro Leu Lys

260 265 270

Glu Gly Tyr Val Arg Ile Asn Tyr Leu Ser Ser Ser Ser Asn Tyr Asp

275 280 285

His Leu Ser Ala Trp Leu Phe Lys Asp Val Ala Thr Xaa Ser Thr Thr

290 295 300

Trp Pro Asp Gly Ser Asn Phe Val Asn Gln Gly Leu Tyr Gly Arg Tyr

305 310 315 320

Ile Asp Val Ser Leu Lys Thr Asn Ala Lys Glu Ile Gly Phe Leu Ile

325 330 335

Leu Asp Glu Ser Lys Thr Gly Asp Ala Val Lys Val Gln Pro Asn Asp

340 345 350

Tyr Val Phe Arg Asp Leu Ala Asn His Asn Gln Ile Phe Val Lys Asp

355 360 365

Lys Asp Pro Lys Val Tyr Asn Asn Pro Tyr Tyr Ile Asp Gln Val Gln

370 375 380

Leu Lys Asp Ala Gln Gln Ile Asp Leu Thr Ser Ile Gln Ala Ser Phe

385 390 395 400

Thr Thr Leu Asp Gly Val Asp Lys Thr Glu Ile Leu Lys Glu Leu Lys

405 410 415

Val Thr Asp Lys Asn Gln Asn Ala Ile Gln Ile Ser Asp Ile Thr Leu

420 425 430

Asp Thr Ser Lys Ser Leu Leu Ile Ile Lys Gly Asp Phe Asn Pro Lys

435 440 445

Gln Gly His Phe Asn Ile Ser Tyr Asn Gly Asn Asn Val Met Thr Arg

450 455 460

Gln Ser Trp Glu Phe Lys Asp Gln Leu Tyr Ala Tyr Ser Gly Asn Leu

465 470 475 480

Gly Ala Val Leu Asn Gln Asp Gly Ser Lys Val Glu Ala Ser Leu Trp

485 490 495

Ser Pro Ser Ala Asp Ser Val Thr Met Ile Ile Tyr Asp Lys Asp Asn

500 505 510

Gln Asn Arg Val Val Ala Thr Thr Pro Leu Val Lys Asn Asn Lys Gly

515 520 525

Val Trp Gln Thr Ile Leu Asp Thr Lys Leu Gly Ile Lys Asn Tyr Thr

530 535 540

Gly Tyr Tyr Tyr Leu Tyr Glu Ile Lys Arg Gly Lys Asp Lys Val Lys

545 550 555 560

Ile Leu Asp Pro Tyr Ala Lys Ser Leu Ala Glu Trp Asp Ser Asn Thr

565 570 575

Val Asn Asp Asp Ile Lys Thr Ala Lys Ala Ala Phe Val Asn Pro Ser

580 585 590

Gln Leu Gly Pro Gln Asn Leu Ser Phe Ala Lys Ile Ala Asn Phe Lys

595 600 605

Gly Arg Gln Asp Ala Val Ile Tyr Glu Ala His Val Arg Asp Phe Thr

610 615 620

Ser Asp Arg Ser Leu Asp Gly Lys Leu Lys Asn Gln Phe Gly Thr Phe

625 630 635 640

Ala Ala Phe Ser Glu Lys Leu Asp Tyr Leu Gln Lys Leu Gly Val Thr

645 650 655

His Ile Gln Leu Leu Pro Val Leu Ser Tyr Phe Tyr Val Asn Glu Met

660 665 670

Asp Lys Ser Arg Ser Thr Ala Tyr Thr Ser Ser Asp Asn Asn Tyr Asn

675 680 685

Trp Gly Tyr Asp Pro Gln Ser Tyr Phe Ala Leu Ser Gly Met Tyr Ser

690 695 700

Glu Lys Pro Lys Asp Pro Ser Ala Arg Ile Ala Glu Leu Lys Gln Leu

705 710 715 720

Ile His Asp Ile His Lys Arg Gly Met Gly Val Ile Leu Asp Val Val

725 730 735

Tyr Asn His Thr Ala Lys Thr Tyr Leu Phe Glu Asp Ile Glu Pro Asn

740 745 750

Tyr Tyr His Phe Met Asn Glu Asp Gly Ser Pro Arg Glu Ser Phe Gly

755 760 765

Gly Gly Arg Leu Gly Thr Thr His Ala Met Ser Arg Arg Val Leu Val

770 775 780

Asp Ser Ile Lys Tyr Leu Thr Ser Glu Phe Lys Val Asp Gly Phe Arg

785 790 795 800

Phe Asp Met Met Gly Asp His Asp Ala Ala Ala Ile Glu Leu Ala Tyr

805 810 815

Lys Glu Ala Lys Ala Ile Asn Pro Asn Met Ile Met Ile Gly Glu Gly

820 825 830

Trp Arg Thr Phe Gln Gly Asp Gln Gly Gln Pro Val Lys Pro Ala Asp

835 840 845

Gln Asp Trp Met Lys Ser Thr Asp Thr Val Gly Val Phe Ser Asp Asp

850 855 860

Ile Arg Asn Ser Leu Lys Ser Gly Phe Pro Asn Glu Gly Thr Pro Ala

865 870 875 880

Phe Ile Thr Gly Gly Pro Gln Ser Leu Gln Gly Ile Phe Lys Asn Ile

885 890 895

Lys Ala Gln Pro Gly Asn Phe Glu Ala Asp Ser Pro Gly Asp Val Val

900 905 910

Gln Tyr Ile Ala Ala His Asp Asn Leu Thr Leu His Asp Val Ile Ala

915 920 925

Lys Ser Ile

930

<210>27

<211>5607

<212>DNA

<213>链球菌

<220>

<221>CDS

<222>(2)...(301)

<400>27

a att caa agt ttg aca gaa ggt caa ctt cgt tct gat atc cct gag ttc 49

Ile Gln Ser Leu Thr Glu Gly Gln Leu Arg Ser Asp Ile Pro Glu Phe

1 5 10 15

cgt gct ggt gat act gta cgt gtt cac gct aaa gtt gtt gaa ggt act 97

Arg Ala Gly Asp Thr Val Arg Val His Ala Lys Val Val Glu Gly Thr

20 25 30

cgc gaa cgt att cag atc ttt gaa ggt gtt gtt atc tca cgt aaa ggt 145

Arg Glu Arg Ile Gln Ile Phe Glu Gly Val Val Ile Ser Arg Lys Gly

35 40 45

caa gga atc tca gaa atg tac aca gta cgt aaa att tct ggt ggt atc 193

Gln Gly Ile Ser Glu Met Tyr Thr Val Arg Lys Ile Ser Gly Gly Ile

50 55 60

ggt gta gag cgt aca ttc cca att cac act cct cgt gtt gat aaa atc 241

Gly Val Glu Arg Thr Phe Pro Ile His Thr Pro Arg Val Asp Lys Ile

65 70 75 80

gaa gtt gtt cgt tat ggt aaa gta cgt cgt gct aaa ctt tac tac tta 289

Glu Val Val Arg Tyr Gly Lys Val Arg Arg Ala Lys Leu Tyr Tyr Leu

85 90 95

cgc gca ttg caa ggtaaagctg cacgtattaa agaaatccgt cgttaatttt 341

Arg Ala Leu Gln

100

gatgatcaga ttttaaaaat gcttggttgt ttgaggatag taactatgtt ttaaaactgg 401

acaaccaaga cgtaaaaaat ctgcctgtgg gcagtttttt tactaggtcc ccttagttca 461

atggatataa caactccctc ctaaggagta attgctggtt cgattccggc aggggacata 521

ttcattgcat gtaaatagcg gtttagagct attttgcccc aaatttctct gattaagttt 581

atcgttccta tctttttgtt cttgtaattg atgtgcgtaa acttctaaag tgatatttaa 641

attctcgtga tctaaaactt gagagatgga aattagatag cttgcaaatg tatgcctgag 701

agagtgcact cgtacctcgc gaccagttat ttttcggata gttttattga ctgcattatt 761

tgaaagtttg tcgaataatc tgtcgttttt attttttgta aattcatgca aaaaaaataa 821

tgtatcattg tcaattggta tatttctgat actacttttg ttttttgttg gcaggtatct 881

ttggttgaaa tgataatccc aagttttatt aattgataaa tatttgttag tgtaatcaat 941

atcattaact gttaaaccta aacattcagc gaagcgcatg ccagttttag cgatgaggta 1001

taacgctgca tacgattgat gttgtgattt ttctttacaa atttttatca agcgtaagta 1061

ttcattggtt tcaagaaatt ttatctctat ttacgcccct tattttttgc tttaacctta 1121

gtgaataaac aaaaattttt ttctatatat ccctcgtgaa cagccatgga tacgcaggct 1181

tttacatgta tgttaaaacg ctttactgta tcttgcacat gcgtttgact ataatgattt 1241

atgacttgtt gatatttagt ggaagtaata ttgcaaagta atatatttcc tattatatgt 1301

ttatacgata tccgatattc ccacccgttg tcgcgtttac ggaaatacgc cattgatata 1361

ctccacatta gctaaagaac agggtgttca aggctacctt gatggaaaag gctctcttag 1421

agatatttgt aaatggtatg atatctcaag tcgctctgtt ctccaaaagt ggataaaacg 1481

gtatactagt ggtgaagact tgaaagccac tagtagagga tatagccgta tgaaacaagg 1541

aaggcaagcc acatttgaag aacgtgtaga gattgttaac tacaccattg cccatgggaa 1601

agactatcaa gcagctattg agaagtttgg tgtttcctac caacaaattt attcttgggt 1661

gcgtaagctt gagaagaatg gctcacaagg tttggttgat agacgtgtga aagggttgga 1721

gagtaggcct gatttaaccg agattgagca actttaactc aagattaaac aattggagga 1781

acgtaatcgt ctcttagaaa tcgaggttag tttactaaaa aagttagaag acatcaaacg 1841

aggaaacaga cggtaagact aggtaagcat ttagcggagt tccaagtaat caagaattat 1901

tacgatgagg aatctaatgt gcctattcag gccttatgcc aactcttgaa ggggtctcgt 1961

tcaggctatt acaagtggct caatcgtcaa aaaacagatt ttgagacaaa aaatacaaag 2021

ctaatggcta aaatcaagga acttcgtaga ctctacaatg gtatcttagg ttatcgccgt 2081

atgacaacat ttattaatcg tcaacttggg acaacttaaa acaagaaacg gattcgttga 2141

ttgatgaaca ttctggggat tagttcagtc attcgtcgtg ttagccatgc ttgtacaaaa 2201

gctggtgaca gattttacga agaaaatatt cttaatcgtg aatttacagc cacagctcat 2261

aaccagaaac ggtgcacaga tgtcacctat cttcaatacg gtctgggagc taaagcttat 2321

ctcagcgcga ttaaagacct gtataacggt tctattatcg cttatgagat tagtcacaac 2381

aatgaaatcc acttgttatg aagaccatta aaaaggggct agagctcaat ccaggagcca 2441

cacctatcat ccatagcgat tgaggtagtc aatatacttc caaagaatac cgttatatca 2501

tacaacaagc tggtctgacc ttatccatgt cccggattgg caaatgtatt gataatgcac 2561

caactgaaag tttctttggg tttttcaaga ctgagtctta ccaccttaag aaatacaact 2621

cttatgatga gttggtcaat gatgtggcac gttatatcga attctacaac acacaacgtt 2681

atcaatcaaa attaaacaac ctgactcctc tagaattcag gaatcaggtt gcataactta 2741

tcttttatta tttgactgtc tacttgacag ggagccgttc agattgctta acctttctaa 2801

atttgctaaa atagctacaa gaaaacgagc catttaatgc ttatttctta tactgtcttg 2861

cctcacgctc tcctcgacca aaaattgagc gtgaggcttt ttgtttcatt aaacgatgat 2921

atttccatat tcatcagttt gttttccgag agccatcaaa gcttcgataa ggtcgataat 2981

tccaggaata aaggtaatac taaaaataat atataaaaaa acctggccta tttttcctgc 3041

gtaaaattta tgcgctccaa tgccgcccaa aagaacgtta ataaaacata aactactatg 3101

ttagcataag actttatttt tacaactgaa tttcatataa atggattaga gtaagggata 3161

aaagaaatta gcatagctct tttgaaaata aaaaaattaa tataatatgg aaaaaatttt 3221

atttcataaa cgtttcataa aaggtatgta atctagtatt taggcaacac tattttgtca 3281

ctggtgtcta gtaacttata gattgataat tttactagta aacgtaattc ttcgctttaa 3341

gagttaaatg tctatttatt gtaagctaaa ttgggaggtg aacttatgta aaattagata 3401

ggtactgtca agtacgggat gattattgaa acagccagta tgcatcataa aatctgtatt 3461

gcttaataac tatttcctta accagacatc agttcattgt ttatcatcgc taccctaagt 3521

ctagtttttt caatagagca ttaggtagtt tttgataata aaactatata aacatgagaa 3581

ttagatttcg tattgcattc ttcataatga gttatttgag attttccttt gaataaatag 3641

atacgaaatt cagtaacttc atatataaac ggctctatca ttgagatagt ttgtcaaatg 3701

aagaaatttt taatggaaat agttttaaaa acattagttg taggcgatgt aaaaatatta 3761

atccagtgga tgcaatagtt gcggagtaaa aatagagagg agtaattagg aagtgataaa 3821

aaatgctata gcatatatta ccagaaaaaa aaatagaaca cttattatat ttgctatttt 3881

aacaattgtt ctttcttgct tgtattcatg tttaacaata atgaaatcaa gtaatgaaat 3941

agaaaaggct ttatatgaaa gttctaattc ttcaatatca attacaaaaa aagatggtaa 4001

atattttaat attaatcaat ttaagaatat tgaaaaaata aaagaggttg aagaaaaaat 4061

atttcaatat gatggattag caaaattgaa agatcttaaa gtagttagtg gtgagcaaag 4121

tataaataga gaagatttat ctgacgaatt taaaaatgtt gtttcactag aagctacaag 4181

taatactaaa agaaatcttt tatttagtag tggagtattt agttttaaag aaggaaaaaa 4241

tatagaagaa aatgataaga attcaattct tgttcatgaa gaatttgcta aacaaaacaa 4301

actaaaattg ggtgatgaaa ttgatcttga attactagat acggaaaaaa gtggaaaaat 4361

aaaaagtcat aaatttaaaa ttataggaat cttttctggt aaaaaacagg aaacatatac 4421

aggattatca tctgatttta gcgaaaatat ggtttttgta gattattcaa ctagccaaga 4481

aatattaaat aaatcagaga ataatagaat tgcaaataaa attttaatgt attctggtag 4541

tttagaatct acagagcttg ccttaaacaa attgaaagac tttaaaattg ataagtcaaa 4601

gtattctatt aagaaagata ataaagcatt cgaagagtct ttagagtcag tgagtggaat 4661

aaaacatata attaaaataa tgacttattc gattatgtta ggtggaatag ttgttctttc 4721

attaatcttg attctatggt taagagaaag aatttatgaa ataggtatat ttttatctat 4781

tggaacaact aagatacaaa ttataaggca atttatattt gagttaatat tcatatcaat 4841

accaagtata atatcctcct tatttttagg gaatctacta ttaaaagtaa ttgtagaagg 4901

atttattaac tcagagaact caatgatttt cggtggaagt ttaataaata aaagcagttt 4961

tatgttaaac ataacaacac ttgcagaaag ttatttaata ttaataagta ttattgtttt 5021

atcagttgta atggcctctt cattaatatt atttaagaaa ccacaagaaa tattatcaaa 5081

aataagttag gagcaaataa tggatatatt agaaataaag aatgtaaatt acagttacgc 5141

aaattctaaa gaaaaagttt tgtcaggagt aaatcaaaaa tttgaacttg gaaagtttta 5201

tgcgatagta gggaagtcag gaacaggaaa atccacactt ctttccttac ttgcaggact 5261

tgataaagtt caaacaggaa aaatcttgtt taagaatgaa gatatagaaa agaaaggata 5321

tagtaatcac agaaaaaata atatatcttt ggtatttcaa aattataatt taatagatta 5381

tttatcgccg attgaaaata ttagactagt aaataaatca gtagatgaga gtatcttgtt 5441

cgaattaggt ttagataaaa aacaaataaa aagaaatgtt atgaaattat ctggtggtca 5501

gcaacaaagg gtagctattg ctagggcact ggtatcagat gccccaataa tactagctga 5561

tgagcctacc ggtaacctag acagtgttac tgctggagaa ataatt 5607

<210>28

<211>111

<212>蛋白质

<213>链球菌

<400>28

Ile Gln Ser Leu Thr Glu Gly Gln Leu Arg Ser Asp Ile Pro Glu Phe

1 5 10 15

Arg Ala Gly Asp Thr Val Arg Val His Ala Lys Val Val Glu Gly Thr

20 25 30

Arg Glu Arg Ile Gln Ile Phe Glu Gly Val Val Ile Ser Arg Lys Gly

35 40 45

Gln Gly Ile Ser Glu Met Tyr Thr Val Arg Lys Ile Ser Gly Gly Ile

50 55 60

Gly Val Glu Arg Thr Phe Pro Ile His Thr Pro Arg Val Asp Lys Ile

65 70 75 80

Glu Val Val Arg Tyr Gly Lys Val Arg Arg Ala Lys Leu Tyr Tyr Leu

85 90 95

Arg Ala Leu Gln Gly Lys Ala Ala Arg Ile Lys Glu Ile Arg Arg

100 105 110

<210>29

<211>173

<212>蛋白质

<213>链球菌

<400>29

Met Arg Phe Ala Glu Cys Leu Gly Leu Thr Val Asn Asp Ile Asp Tyr

1 5 10 15

Thr Asn Lys Tyr Leu Ser Ile Asn Lys Thr Trp Asp Tyr His Phe Asn

20 25 30

Gln Arg Tyr Leu Pro Thr Lys Asn Lys Ser Ser Ile Arg Asn Ile Pro

35 40 45

Ile Asp Asn Asp Thr Leu Phe Phe Leu His Glu Phe Thr Lys Asn Lys

50 55 60

Asn Asp Arg Leu Phe Asp Lys Leu Ser Asn Asn Ala Val Asn Lys Thr

65 70 75 80

Ile Arg Lys Ile Thr Gly Arg Glu Val Arg Val His Ser Leu Arg His

85 90 95

Thr Phe Ala Ser Tyr Leu Ile Ser Ile Ser Gln Val Leu Asp His Glu

100 105 110

Asn Leu Asn Ile Thr Leu Glu Val Tyr Ala His Gln Leu Gln Glu Gln

115 120 125

Lys Asp Arg Asn Asp Lys Leu Asn Gln Arg Asn Leu Gly Gln Asn Ser

130 135 140

Ser Lys Pro Leu Phe Thr Cys Asn Glu Tyr Val Pro Cys Arg Asn Arg

145 150 155 160

Thr Ser Asn Tyr Ser Leu Gly Gly Ser Cys Tyr Ile His

165 170

<210>30

<211>389

<212>蛋白质

<213>链球菌

<400>30

Met Lys Ser Ser Asn Glu Ile Glu Lys Ala Leu Tyr Glu Ser Ser Asn

1 5 10 15

Ser Ser Ile Ser Ile Thr Lys Lys Asp Gly Lys Tyr Phe Asn Ile Asn

20 25 30

Gln Phe Lys Asn Ile Glu Lys Ile Lys Glu Val Glu Glu Lys Ile Phe

35 40 45

Gln Tyr Asp Gly Leu Ala Lys Leu Lys Asp Leu Lys Val Val Ser Gly

50 55 60

Glu Gln Ser Ile Asn Arg Glu Asp Leu Ser Asp Glu Phe Lys Asn Val

65 70 75 80

Val Ser Leu Glu Ala Thr Ser Asn Thr Lys Arg Asn Leu Leu Phe Ser

85 90 95

Ser Gly Val Phe Ser Phe Lys Glu Gly Lys Asn Ile Glu Glu Asn Asp

100 105 110

Lys Asn Ser Ile Leu Val His Glu Glu Phe Ala Lys Gln Asn Lys Leu

115 120 125

Lys Leu Gly Asp Glu Ile Asp Leu Glu Leu Leu Asp Thr Glu Lys Ser

130 135 140

Gly Lys Ile Lys Ser His Lys Phe Lys Ile Ile Gly Ile Phe Ser Gly

145 150 155 160

Lys Lys Gln Glu Thr Tyr Thr Gly Leu Ser Ser Asp Phe Ser Glu Asn

165 170 175

Met Val Phe Val Asp Tyr Ser Thr Ser Gln Glu Ile Leu Asn Lys Ser

180 185 190

Glu Asn Asn Arg Ile Ala Asn Lys Ile Leu Met Tyr Ser Gly Ser Leu

195 200 205

Glu Ser Thr Glu Leu Ala Leu Asn Lys Leu Lys Asp Phe Lys Ile Asp

210 215 220

Lys Ser Lys Tyr Ser Ile Lys Lys Asp Asn Lys Ala Phe Glu Glu Ser

225 230 235 240

Leu Glu Ser Val Ser Gly Ile Lys His Ile Ile Lys Ile Met Thr Tyr

245 250 255

Ser Ile Met Leu Gly Gly Ile Val Val Leu Ser Leu Ile Leu Ile Leu

260 265 270

Trp Leu Arg Glu Arg Ile Tyr Glu Ile Gly Ile Phe Leu Ser Ile Gly

275 280 285

Thr Thr Lys Ile Gln Ile Ile Arg Gln Phe Ile Phe Glu Leu Ile Phe

290 295 300

Ile Ser Ile Pro Ser Ile Ile Ser Ser Leu Phe Leu Gly Asn Leu Leu

305 310 315 320

Leu Lys Val Ile Val Glu Gly Phe Ile Asn Ser Glu Asn Ser Met Ile

325 330 335

Phe Gly Gly Ser Leu Ile Asn Lys Ser Ser Phe Met Leu Asn Ile Thr

340 345 350

Thr Leu Ala Glu Ser Tyr Leu Ile Leu Ile Ser Ile Ile Val Leu Ser

355 360 365

Val Val Met Ala Ser Ser Leu Ile Leu Phe Lys Lys Pro Gln Glu Ile

370 375 380

Leu Ser Lys Ile Ser

385

<210>31

<211>169

<212>蛋白质

<213>链球菌

<400>31

Met Asp Ile Leu Glu Ile Lys Asn Val Asn Tyr Ser Tyr Ala Asn Ser

1 5 10 15

Lys Glu Lys Val Leu Ser Gly Val Asn Gln Lys Phe Glu Leu Gly Lys

20 25 30

Phe Tyr Ala Ile Val Gly Lys Ser Gly Thr Gly Lys Ser Thr Leu Leu

35 40 45

Ser Leu Leu Ala Gly Leu Asp Lys Val Gln Thr Gly Lys Ile Leu Phe

50 55 60

Lys Asn Glu Asp Ile Glu Lys Lys Gly Tyr Ser Asn His Arg Lys Asn

65 70 75 80

Asn Ile Ser Leu Val Phe Gln Asn Tyr Asn Leu Ile Asp Tyr Leu Ser

85 90 95

Pro Ile Glu Asn Ile Arg Leu Val Asn Lys Ser Val Asp Glu Ser Ile

100 105 110

Leu Phe Glu Leu Gly Leu Asp Lys Lys Gln Ile Lys Arg Asn Val Met

115 120 125

Lys Leu Ser Gly Gly Gln Gln Gln Arg Val Ala Ile Ala Arg Ala Leu

130 135 140

Val Ser Asp Ala Pro Ile Ile Leu Ala Asp Glu Pro Thr Gly Asn Leu

145 150 155 160

Asp Ser Val Thr Ala Gly Glu Ile Ile

165

<210>32

<211>4171

<212>DNA

<213>链球菌

<400>32

catatgacaa tatttttcaa agtctacatc acttactcgc ctgtcgtgga aaatctggca 60

atacattaat cgaccaatta gttgctgatg gtttacttca tgcagataat cactaccatt 120

ttttcaatgg gaagtctctg gccactttca atactaacca attgattcgc gaagttgtct 180

atgttgaaat atccttagat actatgtcta gtggtgaaca tgatttagta aaagttaaca 240

ttatcagacc cactaccgag catactatcc ccacgatgat gacagctagc ccctatcatc 300

aaggtatcaa tgatcctgcc gcagaccaaa aaacatacca aatggagggt gcgctagcag 360

ttaaacagcc taaacacata caagttgaca caaaaccatt taaagaagaa gtaaaacatc 420

cttcaaaatt acccatcagc cctgcaactg aaagcttcac acacattgac agttatagtc 480

tcaatgacta ttttctttct cgtggttttg ctaatatata cgtttcaggt gtgggtactg 540

ctggctctac gggtttcatg accagtgggg attaccaaca aatacaaagc tttaaagcag 600

tcattgattg gttaaatggt aaggttactg cattcacaag tcataaacga gataaacaag 660

tcaaggctga ttggtcaaac ggccttgtag caaccacagg taaatcttat ctcggtacca 720

tgtcaactgg tttagcaaca actggcgttg aggggctgaa agtcattatc gctgaagccg 780

caatctccac atggtatgat tattatcgag aaaatgggct tgtgtgtagt ccaggcggct 840

accccggtga agatttagac gttttaacag aattaacata ctcacgaaac ctcttagctg 900

gtgattacat caaaaacaac gattgctatc aagcattgtt aaatgaacaa tcaaaagcaa 960

ttgaccgtca aagtggggat tacaaccaat actggcatga ccgtaattac ctaactcacg 1020

tcaataatgt caaaagtcga gtagtttaca ctcatggact acaggattgg aatgttaagc 1080

caagacatgt ctacaaagtt ttcaatgcat tgcctcaaac catcaaaaaa cacctttttt 1140

tacatcaagg tcaacatgtg tatatgcata attggcagtc gattgatttt cgtgaaagca 1200

tgaatgcctt actaagccaa gaactacttg gcattgacaa tcatttccaa ttagaagagg 1260

tcatttggca agataatact actgagcaaa cttggcaagt tttagatgct ttcggaggaa 1320

accatcaaga gcaaattggt ttaggtgata gtaaaaaact tattgataac cattatgaca 1380

aagaagcctt tgatacttat tgtaaagact tcaatgtgtt caaaaatgat cttttcaagg 1440

gaaataataa aaccaatcaa atcactatta atcttcctct aaagaaaaat tatctcctga 1500

atggacagtg caaactccat ctacgtgtta aaactagtga caaaaaggcc attttatcag 1560

cccaaatctt agactatggt cctaaaaaac gattcaaaga tacaccaacc atcaaattct 1620

taaacagcct tgataatggt aaaaattttg ccagagaagc tttacgtgaa ctcccgttta 1680

ctaaagatca ttatcgtgtc atcagtaaag gtgtcttgaa ccttcaaaat cgtacagact 1740

tacttacaat tgaggctatc gagccagaac aatggtttga tatcgagttt agcctccaac 1800

caagtatata tcaattgagt aaaggtgata atctaaggat tatcctttat acaactgatt 1860

ttgaacatac cattcgagat aatgctagtt actctataac agtagatttg agtcaatctt 1920

atttaactat cccaactaat caaggaaatt aacttatgaa acttcttact aaagaacggt 1980

ttgatgattc tcaacacttt tggtaccaga tcaatttatt acaagagagt aacttcggag 2040

cagtttttga ccatgataat aaaaacattc cacaggttgt tgcaactatt gttgatgatt 2100

tacaaggttc cggaagttcg aatcatttct ggtattttgg caatactact gatacttcca 2160

tccttatgat tgctcattta aatcgaaaat tctatattca ggttaattta aaggactttg 2220

actttgcact caatttaata gctataaata attggaagag tctcctccaa actcaacttg 2280

aagctctaaa cgatacccta gcaatatttc aataaataag gtagaatgga gtgacaaagc 2340

aacgcgaggg agactgatta atgtcatctt attggaataa ctatcctgaa cttaaaaaaa 2400

atattgatga aaccaatcaa ctaattcaag aaagaataca ggtcagaaat aaagatattg 2460

aagcggcgct aagccaactc acagctgcgg gaggaaaaca gctcagacca gcattctttt 2520

accttttttc tcaacttggt aataaggaga atcaagatac tcagcaacta aagaaaatcg 2580

ctgcttcttt agaaatcctt cacgttgcta cattaatcca tgatgatgtc attgatgact 2640

caccactaag acgtggaaat atgaccattc aaagcaagtt tggcaaagac atcgcagttt 2700

atactgggga tttacttttc acagtctttt tcgatcttat tttagaatct atgactgata 2760

caccatttat gaggattaat gcaaaatcta tgcgtaaaat tctcatggga gaattggacc 2820

agatgcacct tcgttacaat caacaacaag gtatccatca ctatttacgt gcgatttcag 2880

gtaagacagc cgaactcttt aaattagcta gcaaagaagg agcttacttt ggtggtgcag 2940

agaaggaggt tgttcgtcta gcaggccata tcggctttaa cattggtatg acattccaaa 3000

ttttggatga tatcctggat tatactgcag ataaaaaaac atttaataag cctgtcttag 3060

aggatttaac acaaggcgtt tacagccttc ctctacttct tgccattgaa gaaaatcctg 3120

atattttcaa acctatttta gataaaaaaa cagatatggc tactgaagac atggaaaaaa 3180

ttgcttatct cgtcgtttcc catagaggtg ttgacaaagc tcgccatcta gctcgtaaat 3240

ttactgagaa agctattagt gacataaata agctacccca gaactctgca aaaaaacagt 3300

tgctacaatt aactaattac cttttaaaac gcaaaattta aataataaaa aaacattcca 3360

caatgctaga aaagcagtta gggaatgttt ttttattatc atttatttat cgcacctatc 3420

aatcatcata gatcaccatc atcagcggct ttcagctgac ggtaacgttg actactttga 3480

gacaattctt gaggagaacc ttccaactct aattgcccat tttctataaa taagatacga 3540

tcagcatgtt caataccttt taagtgatgt gtaatccaaa ctaaggtctt accttccaat 3600

tctttcataa atacccttag taaggcttgt tcagtaatag gatcaagtcc aacagttggc 3660

tcatctaaga taacaattgg gacatctttt agtaagattc tagccaaagc aattctatgc 3720

ctttcgccac ctgaaaacct aagtccagct tcatcaacca ttgtatagag accatctgat 3780

aaatcagtga ccatctcttt caatccaact cgttcaagaa ctttccatac atcttcttca 3840

ctagcatctt ggtttccaat gcgaatgtta tttagcaggg ttgtattaaa aaggtagggc 3900

gcttgttgta tcactccaat atagttagaa atgcaatcac caactattga aacatcagca 3960

ccgcctaggg taatcttccc ttgacttgct ttcaagtcgc cacgaagtag actagctaag 4020

gtactcttgc cagaaccact ccgccctaaa atagcaattt tttctccttc tttaatatcc 4080

aaatctaaat gatgcaaaac ccatttctct tgtggcttat actggaaact taaattcttg 4140

acggaaaaat catatggctt attaggcaat t 4171

<210>33

<211>649

<212>蛋白质

<213>链球菌

<400>33

Tyr Asp Asn Ile Phe Gln Ser Leu His His Leu Leu Ala Cys Arg Gly

1 5 10 15

Lys Ser Gly Asn Thr Leu Ile Asp Gln Leu Val Ala Asp Gly Leu Leu

20 25 30

His Ala Asp Asn His Tyr His Phe Phe Asn Gly Lys Ser Leu Ala Thr

35 40 45

Phe Asn Thr Asn Gln Leu Ile Arg Glu Val Val Tyr Val Glu Ile Ser

50 55 60

Leu Asp Thr Met Ser Ser Gly Glu His Asp Leu Val Lys Val Asn Ile

65 70 75 80

Ile Arg Pro Thr Thr Glu His Thr Ile Pro Thr Met Met Thr Ala Ser

85 90 95

Pro Tyr His Gln Gly Ile Asn Asp Pro Ala Ala Asp Gln Lys Thr Tyr

100 105 110

Gln Met Glu Gly Ala Leu Ala Val Lys Gln Pro Lys His Ile Gln Val

115 120 125

Asp Thr Lys Pro Phe Lys Glu Glu Val Lys His Pro Ser Lys Leu Pro

130 135 140

Ile Ser Pro Ala Thr Glu Ser Phe Thr His Ile Asp Ser Tyr Ser Leu

145 150 155 160

Asn Asp Tyr Phe Leu Ser Arg Gly Phe Ala Asn Ile Tyr Val Ser Gly

165 170 175

Val Gly Thr Ala Gly Ser Thr Gly Phe Met Thr Ser Gly Asp Tyr Gln

180 185 190

Gln Ile Gln Ser Phe Lys Ala Val Ile Asp Trp Leu Asn Gly Lys Val

195 200 205

Thr Ala Phe Thr Ser His Lys Arg Asp Lys Gln Val Lys Ala Asp Trp

210 215 220

Ser Asn Gly Leu Val Ala Thr Thr Gly Lys Ser Tyr Leu Gly Thr Met

225 230 235 240

Ser Thr Gly Leu Ala Thr Thr Gly Val Glu Gly Leu Lys Val Ile Ile

245 250 255

Ala Glu Ala Ala Ile Ser Thr Trp Tyr Asp Tyr Tyr Arg Glu Asn Gly

260 265 270

Leu Val Cys Ser Pro Gly Gly Tyr Pro Gly Glu Asp Leu Asp Val Leu

275 280 285

Thr Glu Leu Thr Tyr Ser Arg Asn Leu Leu Ala Gly Asp Tyr Ile Lys

290 295 300

Asn Asn Asp Cys Tyr Gln Ala Leu Leu Asn Glu Gln Ser Lys Ala Ile

305 310 315 320

Asp Arg Gln Ser Gly Asp Tyr Asn Gln Tyr Trp His Asp Arg Asn Tyr

325 330 335

Leu Thr His Val Asn Asn Val Lys Ser Arg Val Val Tyr Thr His Gly

340 345 350

Leu Gln Asp Trp Asn Val Lys Pro Arg His Val Tyr Lys Val Phe Asn

355 360 365

Ala Leu Pro Gln Thr Ile Lys Lys His Leu Phe Leu His Gln Gly Gln

370 375 380

His Val Tyr Met His Asn Trp Gln Ser Ile Asp Phe Arg Glu Ser Met

385 390 395 400

Asn Ala Leu Leu Ser Gln Glu Leu Leu Gly Ile Asp Asn His Phe Gln

405 410 415

Leu Glu Glu Val Ile Trp Gln Asp Asn Thr Thr Glu Gln Thr Trp Gln

420 425 430

Val Leu Asp Ala Phe Gly Gly Asn His Gln Glu Gln Ile Gly Leu Gly

435 440 445

Asp Ser Lys Lys Leu Ile Asp Asn His Tyr Asp Lys Glu Ala Phe Asp

450 455 460

Thr Tyr Cys Lys Asp Phe Asn Val Phe Lys Asn Asp Leu Phe Lys Gly

465 470 475 480

Asn Asn Lys Thr Asn Gln Ile Thr Ile Asn Leu Pro Leu Lys Lys Asn

485 490 495

Tyr Leu Leu Asn Gly Gln Cys Lys Leu His Leu Arg Val Lys Thr Ser

500 505 510

Asp Lys Lys Ala Ile Leu Ser Ala Gln Ile Leu Asp Tyr Gly Pro Lys

515 520 525

Lys Arg Phe Lys Asp Thr Pro Thr Ile Lys Phe Leu Asn Ser Leu Asp

530 535 540

Asn Gly Lys Asn Phe Ala Arg Glu Ala Leu Arg Glu Leu Pro Phe Thr

545 550 555 560

Lys Asp His Tyr Arg Val Ile Ser Lys Gly Val Leu Asn Leu Gln Asn

565 570 575

Arg Thr Asp Leu Leu Thr Ile Glu Ala Ile Glu Pro Glu Gln Trp Phe

580 585 590

Asp Ile Glu Phe Ser Leu Gln Pro Ser Ile Tyr Gln Leu Ser Lys Gly

595 600 605

Asp Asn Leu Arg Ile Ile Leu Tyr Thr Thr Asp Phe Glu His Thr Ile

610 615 620

Arg Asp Asn Ala Ser Tyr Ser Ile Thr Val Asp Leu Ser Gln Ser Tyr

625 630 635 640

Leu Thr Ile Pro Thr Asn Gln Gly Asn

645

<210>34

<211>119

<212>蛋白质

<213>链球菌

<400>34

Met Lys Leu Leu Thr Lys Glu Arg Phe Asp Asp Ser Gln His Phe Trp

1 5 10 15

Tyr Gln Ile Asn Leu Leu Gln Glu Ser Asn Phe Gly Ala Val Phe Asp

20 25 30

His Asp Asn Lys Asn Ile Pro Gln Val Val Ala Thr Ile Val Asp Asp

35 40 45

Leu Gln Gly Ser Gly Ser Ser Asn His Phe Trp Tyr Phe Gly Asn Thr

50 55 60

Thr Asp Thr Ser Ile Leu Met Ile Ala His Leu Asn Arg Lys Phe Tyr

65 70 75 80

Ile Gln Val Asn Leu Lys Asp Phe Asp Phe Ala Leu Asn Leu Ile Ala

85 90 95

Ile Asn Asn Trp Lys Ser Leu Leu Gln Thr Gln Leu Glu Ala Leu Asn

100 105 110

Asp Thr Leu Ala Ile Phe Gln

115

<210>35

<211>326

<212>蛋白质

<213>链球菌

<400>35

Met Ser Ser Tyr Trp Asn Asn Tyr Pro Glu Leu Lys Lys Asn Ile Asp

1 5 10 15

Glu Thr Asn Gln Leu Ile Gln Glu Arg Ile Gln Val Arg Asn Lys Asp

20 25 30

Ile Glu Ala Ala Leu Ser Gln Leu Thr Ala Ala Gly Gly Lys Gln Leu

35 40 45

Arg Pro Ala Phe Phe Tyr Leu Phe Ser Gln Leu Gly Asn Lys Glu Asn

50 55 60

Gln Asp Thr Gln Gln Leu Lys Lys Ile Ala Ala Ser Leu Glu Ile Leu

65 70 75 80

His Val Ala Thr Leu Ile His Asp Asp Val Ile Asp Asp Ser Pro Leu

85 90 95

Arg Arg Gly Asn Met Thr Ile Gln Ser Lys Phe Gly Lys Asp Ile Ala

100 105 110

Val Tyr Thr Gly Asp Leu Leu Phe Thr Val Phe Phe Asp Leu Ile Leu

115 120 125

Glu Ser Met Thr Asp Thr Pro Phe Met Arg Ile Asn Ala Lys Ser Met

130 135 140

Arg Lys Ile Leu Met Gly Glu Leu Asp Gln Met His Leu Arg Tyr Asn

145 150 155 160

Gln Gln Gln Gly Ile His His Tyr Leu Arg Ala Ile Ser Gly Lys Thr

165 170 175

Ala Glu Leu Phe Lys Leu Ala Ser Lys Glu Gly Ala Tyr Phe Gly Gly

180 185 190

Ala Glu Lys Glu Val Val Arg Leu Ala Gly His Ile Gly Phe Asn Ile

195 200 205

Gly Met Thr Phe Gln Ile Leu Asp Asp Ile Leu Asp Tyr Thr Ala Asp

210 215 220

Lys Lys Thr Phe Asn Lys Pro Val Leu Glu Asp Leu Thr Gln Gly Val

225 230 235 240

Tyr Ser Leu Pro Leu Leu Leu Ala Ile Glu Glu Asn Pro Asp Ile Phe

245 250 255

Lys Pro Ile Leu Asp Lys Lys Thr Asp Met Ala Thr Glu Asp Met Glu

260 265 270

Lys Ile Ala Tyr Leu Val Val Ser His Arg Gly Val Asp Lys Ala Arg

275 280 285

His Leu Ala Arg Lys Phe Thr Glu Lys Ala Ile Ser Asp Ile Asn Lys

290 295 300

Leu Pro Gln Asn Ser Ala Lys Lys Gln Leu Leu Gln Leu Thr Asn Tyr

305 310 315 320

Leu Leu Lys Arg Lys Ile

325

<210>36

<211>247

<212>蛋白质

<213>链球菌

<400>36

Leu Pro Asn Lys Pro Tyr Asp Phe Ser Val Lys Asn Leu Ser Phe Gln

1 5 10 15

Tyr Lys Pro Gln Glu Lys Trp Val Leu His His Leu Asp Leu Asp Ile

20 25 30

Lys Glu Gly Glu Lys Ile Ala Ile Leu Gly Arg Ser Gly Ser Gly Lys

35 40 45

Ser Thr Leu Ala Ser Leu Leu Arg Gly Asp Leu Lys Ala Ser Gln Gly

50 55 60

Lys Ile Thr Leu Gly Gly Ala Asp Val Ser Ile Val Gly Asp Cys Ile

65 70 75 80

Ser Asn Tyr Ile Gly Val Ile Gln Gln Ala Pro Tyr Leu Phe Asn Thr

85 90 95

Thr Leu Leu Asn Asn Ile Arg Ile Gly Asn Gln Asp Ala Ser Glu Glu

100 105 110

Asp Val Trp Lys Val Leu Glu Arg Val Gly Leu Lys Glu Met Val Thr

115 120 125

Asp Leu Ser Asp Gly Leu Tyr Thr Met Val Asp Glu Ala Gly Leu Arg

130 135 140

Phe Ser Gly Gly Glu Arg His Arg Ile Ala Leu Ala Arg Ile Leu Leu

145 150 155 160

Lys Asp Val Pro Ile Val Ile Leu Asp Glu Pro Thr Val Gly Leu Asp

165 170 175

Pro Ile Thr Glu Gln Ala Leu Leu Arg Val Phe Met Lys Glu Leu Glu

180 185 190

Gly Lys Thr Leu Val Trp Ile Thr His His Leu Lys Gly Ile Glu His

195 200 205

Ala Asp Arg Ile Leu Phe Ile Glu Asn Gly Gln Leu Glu Leu Glu Gly

210 215 220

Ser Pro Gln Glu Leu Ser Gln Ser Ser Gln Arg Tyr Arg Gln Leu Lys

225 230 235 240

Ala Ala Asp Asp Gly Asp Leu

245

<210>37

<211>3480

<212>DNA

<213>链球菌

<400>37

aattctattt ggaggttttt cttgaataaa tggttagtta aggcaagttc cttagttgtt 60

ttaggtggta tggttttatc tgcgggttcc cgagttttag cggatactta tgtccgtcca 120

attgataatg gtagaattac aacaggtttc aatggttatc ctggacattg tggggtggat 180

tatgctgttc cgactggaac gattattagg gcagtggcag atggtactgt gaaatttgca 240

ggagctggag ccaacttttc ttggatgaca gacttagcag gaaattgtgt catgattcaa 300

catgcggatg gaatgcatag tggttacgct catatgtcac gtgtggtggc taggactggg 360

gaaaaagtca aacaaggaga tatcatcggt tacgtaggag caactggtat ggcgacggga 420

cctcaccttc attttgaatt tttaccagct aaccctaatt ttcaaaatgg tttccatgga 480

cgtatcaatc caacgtcact aattgctaac gttgcgacct ttagtggaaa aacgcaagca 540

tcagctccaa gcattaagcc attacaatca gctcctgtac agaatcaatc tagtaaatta 600

aaagtgtatc gagtagacga attacaaaag gttaatggtg tttggttagt caaaaataac 660

accctaacgc cgactgggtt tgattggaac gataatggta taccagcatc agaaattgat 720

gaggttgatg ctaatggtaa tttgacagct gaccaggttc ttcaaaaagg tggttacttt 780

atctttaatc ctaaaactct taagactgta gaaaaaccca tccaaggaac agctggttta 840

acttgggcta agacacgctt tgctaatggt agttcagttt ggcttcgcgt tgacaacagt 900

caagaactgc tttacaaata gtttgaggta ttgattcatt gttttaaatg acagttttgt 960

tactaactaa gtacaatttc tttaaaccgt ctgaaaataa ttttatagtc cagtaaagtg 1020

tgatattata gtctcggact aataaaaagg aaataggaat tgaagcaatg aaaatgaata 1080

aaaaggtact attgacatcg acaatggcag cttcgctatt atcagtcgca agtgttcaag 1140

cacaagaaac agatacgacg tggacagcac gtactgtttc agaggtaaag gctgatttgg 1200

taaagcaaga caataaatca tcatatactg tgaaatatgg tgatacacta agcgttattt 1260

cagaagcaat gtcaattgat atgaatgtct tagcaaaaat taataacatt gcagatatca 1320

atcttattta tcctgagaca acactgacag taacttacga tcagaagagt catactgcca 1380

cttcaatgaa aatagaaaca ccagcaacaa atgctgctgg tcaaacaaca gctactgtgg 1440

atttgaaaac caatcaagtt tctgttgcag accaaaaagt ttctctcaat acaatttcgg 1500

aaggtatgac accagaagca gcaacaacga ttgtttcgcc aatgaagaca tattcttctg 1560

cgccagcttt gaaatcaaaa gaagtattag cacaagagca agctgttagt caagcagcag 1620

ctaatgaaca ggtatcaaca gctcctgtga agtcgattac ttcagaagtt ccagcagcta 1680

aagaggaagt taaaccaact cagacgtcag tcagtcagtc aacaacagta tcaccagctt 1740

ctgttgccgc tgaaacacca gctccagtag ctaaagtagc accggtaaga actgtagcag 1800

cccctagagt ggcaagtgtt aaagtagtca ctcctaaagt agaaactggt gcatcaccag 1860

agcatgtatc agctccagca gttcctgtga ctacgacttc aacagctaca gacagtaagt 1920

tacaagcgac tgaagttaag agcgttccgg tagcacaaaa agctccaaca gcaacaccgg 1980

tagcacaacc agcttcaaca acaaatgcag tagctgcaca tcctgaaaat gcagggctcc 2040

aacctcatgt tgcagcttat aaagaaaaag tagcgtcaac ttatggagtt aatgaattca 2100

gtacataccg tgcaggtgat ccaggtgatc atggtaaagg tttagcagtc gactttattg 2160

taggtaaaaa ccaagcactt ggtaatgaag ttgcacagta ctctacacaa aatatggcag 2220

caaataacat ttcatatgtt atctggcaac aaaagtttta ctcaaataca aatagtattt 2280

atggacctgc taatacttgg aatgcaatgc cagatcgtgg tggcgttact gccaaccatt 2340

atgaccatgt tcacgtatca tttaacaaat aatataaaaa aggaagctat ttggcttctt 2400

ttttatatgc cttgaataga ctttcaaggt tcttatctaa tttttattaa attgaggaga 2460

ttaagctata agtctgaaac tactttcacg ttaaccgtga ctaaatcaaa acgttaaaac 2520

taaaatctaa gtctgtaaag attattgaaa acgctttaaa aacagatata ataaggtttg 2580

tagatatcta aaattaaaaa agataaggaa gtgagaatat gccacatcta agtaaagaag 2640

cttttaaaaa gcaaataaaa aatggcatta ttgtgtcatg tcaagctttg cctggggagc 2700

ctctttatac tgaaagtgga ggtgttatgc ctcttttagc tttggcagct caagaagcag 2760

gagcggttgg tataagagcc aatagtgtcc gcgacattaa ggaaattcaa gaagttacta 2820

atttacctat catcggcatt attaaacgtg aatatcctcc acaagaacca tttatcactg 2880

ctacgatgac agaggtggat caattagcta gtttagatat tgcagtaata gccttagatt 2940

gtacacttag agagcgtcat gatggtttga gtgtagctga gtttattcaa aagataaaag 3000

ggaaatatcc tgaacagttg ctaatggctg atataagtac ttttgaagaa ggtaaaaatg 3060

cttttgaagc aggagttgat tttgtgggta caactctatc tggatacaca gattacagcc 3120

gccaagaaga aggaccggat atagaactcc ttaataagct ttgtcaagcc ggtatagatg 3180

tgattgcgga aggtaaaatt catactccta agcaagctaa tgaaattaat catataggtg 3240

ttgcaggaat tgtagttggt ggtgctatca ctagaccaaa agaaatagcg gagcgtttca 3300

tctcaggact tagttaaaag tgttactcaa aaatcaaaat caaaataaaa aaggggaata 3360

gttatgagta tcaaaaaaag tgtgattggt ttttgcctcg gagctgcagc attatcaatg 3420

tttgcttgtg tagacagtag tcaatctgtt atggctgccg agaaggataa agtcgaaatt 3480

<210>38

<211>306

<212>蛋白质

<213>链球菌

<400>38

Asn Ser Ile Trp Arg Phe Phe Leu Asn Lys Trp Leu Val Lys Ala Ser

1 5 10 15

Ser Leu Val Val Leu Gly Gly Met Val Leu Ser Ala Gly Ser Arg Val

20 25 30

Leu Ala Asp Thr Tyr Val Arg Pro Ile Asp Asn Gly Arg Ile Thr Thr

35 40 45

Gly Phe Asn Gly Tyr Pro Gly His Cys Gly Val Asp Tyr Ala Val Pro

50 55 60

Thr Gly Thr Ile Ile Arg Ala Val Ala Asp Gly Thr Val Lys Phe Ala

65 70 75 80

Gly Ala Gly Ala Asn Phe Ser Trp Met Thr Asp Leu Ala Gly Asn Cys

85 90 95

Val Met Ile Gln His Ala Asp Gly Met His Ser Gly Tyr Ala His Met

100 105 110

Ser Arg Val Val Ala Arg Thr Gly Glu Lys Val Lys Gln Gly Asp Ile

115 120 125

Ile Gly Tyr Val Gly Ala Thr Gly Met Ala Thr Gly Pro His Leu His

130 135 140

Phe Glu Phe Leu Pro Ala Asn Pro Asn Phe Gln Asn Gly Phe His Gly

145 150 155 160

Arg Ile Asn Pro Thr Ser Leu Ile Ala Asn Val Ala Thr Phe Ser Gly

165 170 175

Lys Thr Gln Ala Ser Ala Pro Ser Ile Lys Pro Leu Gln Ser Ala Pro

180 185 190

Val Gln Asn Gln Ser Ser Lys Leu Lys Val Tyr Arg Val Asp Glu Leu

195 200 205

Gln Lys Val Asn Gly Val Trp Leu Val Lys Asn Asn Thr Leu Thr Pro

210 215 220

Thr Gly Phe Asp Trp Asn Asp Asn Gly Ile Pro Ala Ser Glu Ile Asp

225 230 235 240

Glu Val Asp Ala Asn Gly Asn Leu Thr Ala Asp Gln Val Leu Gln Lys

245 250 255

Gly Gly Tyr Phe Ile Phe Asn Pro Lys Thr Leu Lys Thr Val Glu Lys

260 265 270

Pro Ile Gln Gly Thr Ala Gly Leu Thr Trp Ala Lys Thr Arg Phe Ala

275 280 285

Asn Gly Ser Ser Val Trp Leu Arg Val Asp Asn Ser Gln Glu Leu Leu

290 295 300

Tyr Lys

305

<210>39

<211>434

<212>蛋白质

<213>链球菌

<400>39

Met Lys Met Asn Lys Lys Val Leu Leu Thr Ser Thr Met Ala Ala Ser

1 5 10 15

Leu Leu Ser Val Ala Ser Val Gln Ala Gln Glu Thr Asp Thr Thr Trp

20 25 30

Thr Ala Arg Thr Val Ser Glu Val Lys Ala Asp Leu Val Lys Gln Asp

35 40 45

Asn Lys Ser Ser Tyr Thr Val Lys Tyr Gly Asp Thr Leu Ser Val Ile

50 55 60

Ser Glu Ala Met Ser Ile Asp Met Asn Val Leu Ala Lys Ile Asn Asn

65 70 75 80

Ile Ala Asp Ile Asn Leu Ile Tyr Pro Glu Thr Thr Leu Thr Val Thr

85 90 95

Tyr Asp Gln Lys Ser His Thr Ala Thr Ser Met Lys Ile Glu Thr Pro

100 105 110

Ala Thr Asn Ala Ala Gly Gln Thr Thr Ala Thr Val Asp Leu Lys Thr

115 120 125

Asn Gln Val Ser Val Ala Asp Gln Lys Val Ser Leu Asn Thr Ile Ser

130 135 140

Glu Gly Met Thr Pro Glu Ala Ala Thr Thr Ile Val Ser Pro Met Lys

145 150 155 160

Thr Tyr Ser Ser Ala Pro Ala Leu Lys Ser Lys Glu Val Leu Ala Gln

165 170 175

Glu Gln Ala Val Ser Gln Ala Ala Ala Asn Glu Gln Val Ser Thr Ala

180 185 190

Pro Val Lys Ser Ile Thr Ser Glu Val Pro Ala Ala Lys Glu Glu Val

195 200 205

Lys Pro Thr Gln Thr Ser Val Ser Gln Ser Thr Thr Val Ser Pro Ala

210 215 220

Ser Val Ala Ala Glu Thr Pro Ala Pro Val Ala Lys Val Ala Pro Val

225 230 235 240

Arg Thr Val Ala Ala Pro Arg Val Ala Ser Val Lys Val Val Thr Pro

245 250 255

Lys Val Glu Thr Gly Ala Ser Pro Glu His Val Ser Ala Pro Ala Val

260 265 270

Pro Val Thr Thr Thr Ser Thr Ala Thr Asp Ser Lys Leu Gln Ala Thr

275 280 285

Glu Val Lys Ser Val Pro Val Ala Gln Lys Ala Pro Thr Ala Thr Pro

290 295 300

Val Ala Gln Pro Ala Ser Thr Thr Asn Ala Val Ala Ala His Pro Glu

305 310 315 320

Asn Ala Gly Leu Gln Pro His Val Ala Ala Tyr Lys Glu Lys Val Ala

325 330 335

Ser Thr Tyr Gly Val Asn Glu Phe Ser Thr Tyr Arg Ala Gly Asp Pro

340 345 350

Gly Asp His Gly Lys Gly Leu Ala Val Asp Phe Ile Val Gly Lys Asn

355 360 365

Gln Ala Leu Gly Asn Glu Val Ala Gln Tyr Ser Thr Gln Asn Met Ala

370 375 380

Ala Asn Asn Ile Ser Tyr Val Ile Trp Gln Gln Lys Phe Tyr Ser Asn

385 390 395 400

Thr Asn Ser Ile Tyr Gly Pro Ala Asn Thr Trp Asn Ala Met Pro Asp

405 410 415

Arg Gly Gly Val Thr Ala Asn His Tyr Asp His Val His Val Ser Phe

420 425 430

Asn Lys

<210>40

<211>232

<212>蛋白质

<213>链球菌

<400>40

Met Pro His Leu Ser Lys Glu Ala Phe Lys Lys Gln Ile Lys Asn Gly

1 5 10 15

Ile Ile Val Ser Cys Gln Ala Leu Pro Gly Glu Pro Leu Tyr Thr Glu

20 25 30

Ser Gly Gly Val Met Pro Leu Leu Ala Leu Ala Ala Gln Glu Ala Gly

35 40 45

Ala Val Gly Ile Arg Ala Asn Ser Val Arg Asp Ile Lys Glu Ile Gln

50 55 60

Glu Val Thr Asn Leu Pro Ile Ile Gly Ile Ile Lys Arg Glu Tyr Pro

65 70 75 80

Pro Gln Glu Pro Phe Ile Thr Ala Thr Met Thr Glu Val Asp Gln Leu

85 90 95

Ala Ser Leu Asp Ile Ala Val Ile Ala Leu Asp Cys Thr Leu Arg Glu

100 105 110

Arg His Arp Gly Leu Ser Val Ala Glu Phe Ile Gln Lys Ile Lys Gly

115 120 125

Lys Tyr Pro Glu Cln Leu Leu Met Ala Asp Ile Ser Thr Phe Glu Glu

130 135 140

Gly Lys Asn Ala Phe Glu Ala Gly Val Asp Phe Val Gly Thr Thr Leu

145 150 155 160

Ser Gly Tyr Thr Asp Tyr Xaa Arg Gln Glu Glu Gly Pro Asp Ile Glu

165 170 175

Leu Leu Asn Lys Leu Cys Gln Ala Gly Ile Asp Val Ile Ala Glu Gly

180 185 190

Lys Ile His Thr Pro Lys Gln Ala Asn Glu Ile Asn His Ile Gly Val

195 200 205

Ala Gly Ile Val Val Gly Gly Ala Ile Thr Arg Pro Lys Glu Ile Ala

210 215 220

Glu Arg Phe Ile Ser Gly Leu Ser

225 230

<210>41

<211>39

<212>蛋白质

<213>链球菌

<400>41

Met Ser Ile Lys Lys Ser Val Ile Gly Phe Cys Leu Gly Ala Ala Ala

1 5 10 15

Leu Ser Met Phe Ala Cys Val Asp Ser Ser Gln Ser Val Met Ala Ala

20 25 30

Glu Lys Asp Lys Val Glu Ile

35

<210>42

<211>1305

<212>DNA

<213>链球菌

<400>42

atgaaaatga ataaaaaggt actattgaca tcgacaatgg cagcttcgct attatcagtc 60

gcaagtgttc aagcacaaga aacagatacg acgtggacag cacgtactgt ttcagaggta 120

aaggctgatt tggtaaagca agacaataaa tcatcatata ctgtgaaata tggtgataca 180

ctaagcgtta tttcagaagc aatgtcaatt gatatgaatg tcttagcaaa aattaataac 240

attgcagata tcaatcttat ttatcctgag acaacactga cagtaactta cgatcagaag 300

agtcatactg ccacttcaat gaaaatagaa acaccagcaa caaatgctgc tggtcaaaca 360

acagctactg tggatttgaa aaccaatcaa gtttctgttg cagaccaaaa agtttctctc 420

aatacaattt cggaaggtat gacaccagaa gcagcaacaa cgattgtttc gccaatgaag 480

acatattctt ctgcgccagc tttgaaatca aaagaagtat tagcacaaga gcaagctgtt 540

agccaagcag cagctaatga acaggtatca acagctcctg tgaagtcgat tacttcagaa 600

gttccagcag ctaaagagga agttaaacca actcagacgt cagtcagtca gtcaacaaca 660

gtaccaccag cttctgttgc cgctgaaaca ccagctccag tagctaaagt agcaccggta 720

agaactgtag cagcccctag agtggcaagt gttaaagtag tcactcctaa agtagaaact 780

ggtgcatcac cagagcatgt atcagctcca gcagttcctg tgactacgac ttcaacagct 840

acagacagta agttacaagc gactgaagtt aagagcgttc cggtagcaca aaaagctcca 900

acagcaacac cggtagcaca accagcttca acaacaaatg cagtagctgc acatcctgaa 960

aatgcagggc tccaacctca tgttgcagct tataaagaaa aagtagcgtc aacttatgga 1020

gttaatgaat tcagtacata ccgtgcaggt gatccaggtg atcatggtaa aggtttagca 1080

gtcgacttta ttgtaggtaa aaaccaagca cttggtaatg aagttgcaca gtactctaca 1140

caaaatatgg cagcaaataa catttcatat gttatctggc aacaaaagtt ttactcaaat 1200

acaaatagta tttatggacc tgctaatact tggaatgcaa tgccagatcg tggtggcgtt 1260

actgccaacc attatgacca tgttcacgta tcatttaaca aataa 1305

<210>43

<211>1230

<212>DNA

<213>链球菌

<400>43

caagaaacag atacgacgtg gacagcacgt actgtttcag aggtaaaggc tgatttggta 60

aagcaagaca ataaatcatc atatactgtg aaatatggtg atacactaag cgttatttca 120

gaagcaatgt caattgatat gaatgtctta gcaaaaatta ataacattgc agatatcaat 180

cttatttatc ctgagacaac actgacagta acttacgatc agaagagtca tactgccact 240

tcaatgaaaa tagaaacacc agcaacaaat gctgctggtc aaacaacagc tactgtggat 300

ttgaaaacca atcaagtttc tgttgcagac caaaaagttt ctctcaatac aatttcggaa 360

ggtatgacac cagaagcagc aacaacgatt gtttcgccaa tgaagacata ttcttctgcg 420

ccagctttga aatcaaaaga agtattagca caagagcaag ctgttagtca agcagcagct 480

aatgaacagg tatcaacagc tcctgtgaag tcgattactt cagaagttcc agcagctaaa 540

gaggaagtta aaccaactca gacgtcagtc agtcagtcaa caacagtatc accagcttct 600

gttgccgctg aaacaccagc tccagtagct aaagtagcac cggtaagaactgtagcagcc 660

cctagagtgg caagtgttaa agtagtcact cctaaagtag aaactggtgc atcaccagag 720

catgtatcag ctccagcagt tcctgtgact acgacttcaa cagctacaga cagtaagtta 780

caagcgactg aagttaagag cgttccggta gcacaaaaag ctccaacagc aacaccggta 840

gcacaaccag cttcaacaac aaatgcagta gctgcacatc ctgaaaatgc agggctccaa 900

cctcatgttg cagcttataa agaaaaagta gcgtcaactt atggagttaa tgaattcagt 960

acataccgtg caggtgatcc aggtgatcat ggtaaaggtt tagcagtcga ctttattgta 1020

ggtaaaaacc aagcacttgg taatgaagtt gcacagtact ctacacaaaa tatggcagca 1080

aataacattt catatgttat ctggcaacaa aagttttact caaatacaaa tagtatttat 1140

ggacctgcta atacttggaa tgcaatgcca gatcgtggtg gcgttactgc caaccattat 1200

gaccatgttc acgtatcatt taacaaataa 1230

<210>44

<211>409

<212>蛋白质

<213>链球菌

<400>44

Gln Glu Thr Asp Thr Thr Trp Thr Ala Arg Thr Val Ser Glu Val Lys

1 5 10 15

Ala Asp Leu Val Lys Gln Asp Asn Lys Ser Ser Tyr Thr Val Lys Tyr

20 25 30

Gly Asp Thr Leu Ser Val Ile Ser Glu Ala Met Ser Ile Asp Met Asn

35 40 45

Val Leu Ala Lys Ile Asn Asn Ile Ala Asp Ile Asn Leu Ile Tyr Pro

50 55 60

Glu Thr Thr Leu Thr Val Thr Tyr Asp Gln Lys Ser His Thr Ala Thr

65 70 75 80

Ser Met Lys Ile Glu Thr Pro Ala Thr Asn Ala Ala Gly Gln Thr Thr

85 90 95

Ala Thr Val Asp Leu Lys Thr Asn Gln Val Ser Val Ala Asp Gln Lys

100 105 110

Val Ser Leu Asn Thr Ile Ser Glu Gly Met Thr Pro Glu Ala Ala Thr

115 120 125

Thr Ile Val Ser Pro Met Lys Thr Tyr Ser Ser Ala Pro Ala Leu Lys

130 135 140

Ser Lys Glu Val Leu Ala Gln Glu Gln Ala Val Ser Gln Ala Ala Ala

145 150 155 160

Asn Glu Gln Val Ser Thr Ala Pro Val Lys Ser Ile Thr Ser Glu Val

165 170 175

Pro Ala Ala Lys Glu Glu Val Lys Pro Thr Gln Thr Ser Val Ser Gln

180 185 190

Ser Thr Thr Val Ser Pro Ala Ser Val Ala Ala Glu Thr Pro Ala Pro

195 200 205

Val Ala Lys Val Ala Pro Val Arg Thr Val Ala Ala Pro Arg Val Ala

210 215 220

Ser Val Lys Val Val Thr Pro Lys Val Glu Thr Gly Ala Ser Pro Glu

225 230 235 240

His Val Ser Ala Pro Ala Val Pro Val Thr Thr Thr Ser Thr Ala Thr

245 250 255

Asp Ser Lys Leu Gln Ala Thr Glu Val Lys Ser Val Pro Val Ala Gln

260 265 270

Lys Ala Pro Thr Ala Thr Pro Val Ala Gln Pro Ala Ser Thr Thr Asn

275 280 285

Ala Val Ala Ala His Pro Glu Asn Ala Gly Leu Gln Pro His Val Ala

290 295 300

Ala Tyr Lys Glu Lys Val Ala Ser Thr Tyr Gly Val Asn Glu Phe Ser

305 310 315 320

Thr Tyr Arg Ala Gly Asp Pro Gly Asp His Gly Lys Gly Leu Ala Val

325 330 335

Asp Phe Ile Val Gly Lys Asn Gln Ala Leu Gly Asn Glu Val Ala Gln

340 345 350

Tyr Ser Thr Gln Asn Met Ala Ala Asn Asn Ile Ser Tyr Val Ile Trp

355 360 365

Gln Gln Lys Phe Tyr Ser Asn Thr Asn Ser Ile Tyr Gly Pro Ala Asn

370 375 380

Thr Trp Asn Ala Met Pro Asp Arg Gly Gly Val Thr Ala Asn His Tyr

385 390 395 400

Asp His Val His Val Ser Phe Asn Lys

405

Claims

1.分离的多核苷酸，其编码具有选自序列SEQ ID NO：39、SEQ IDNO：41和SEQ ID NO：44的多肽，或者其保守取代的衍生物，其中所述衍生物保持诱导对B组链球菌(BGS)特异性的免疫应答的能力。

2.根据权利要求1的多核苷酸，其中所述多核苷酸编码的多肽与所述序列有至少95％的一致性。

3.分离的多核苷酸，其所编码的多肽能够产生与具有选自下组之序列的多肽有特异结合性的抗体：SEQ ID NO：39、SEQ ID NO：41和SEQ ID NO：44，其中所述多肽保持诱导对B组链球菌(BGS)特异性的免疫应答的能力。

4.与权利要求1的多核苷酸互补的分离的多核苷酸。

5.与权利要求3的多核苷酸互补的分离的多核苷酸。

6.权利要求1的多核苷酸，其中所述多核苷酸是DNA。

7.权利要求3的多核苷酸，其中所述多核苷酸是DNA。

8.权利要求1的多核苷酸，其中所述多核苷酸是RNA。

9.权利要求3的多核苷酸，其中所述多核苷酸是RNA。

10.权利要求1的多核苷酸，其中所述多核苷酸在严格条件下与选自下组之序列杂交：SEQ ID NO：37，SEQ ID NO：42和SEQ ID NO：43。

11.权利要求1的多核苷酸，其中所述多核苷酸在严格条件下与选自下面的一个序列杂交：SEQ ID NO：37，SEQ ID NO：42和SEQ ID NO：43。

12.根据权利要求11的多核苷酸，其在严格条件下与SEQ ID NO：37杂交。

13.根据权利要求11的多核苷酸，其在严格条件下与SEQ ID NO：42杂交。

14.根据权利要求11的多核苷酸，其在严格条件下与SEQ ID NO：43杂交。

15.根据权利要求10的多核苷酸，其中所述多核苷酸与SEQ ID NO：37，SEQ ID NO：42或SEQ ID NO：43有至少95％的互补性。

16.根据权利要求11的多核苷酸，其中所述多核苷酸与SEQ ID NO：37，SEQ ID NO：42和SEQ ID NO：43有至少95％的互补性。

17.包含权利要求1的多核苷酸的载体，其中所述多核苷酸与表达调控区操作连接。

18.包含权利要求3的多核苷酸的载体，其中所述多核苷酸与表达调控区操作连接。

19.用权利要求17的载体转染的宿主细胞。

20.用权利要求18的载体转染的宿主细胞。

21.制备权利要求1中所述多肽的方法，其包括在适合表达权利要求1中所述多肽的条件下培养权利要求19的宿主细胞。

22.制备权利要求3中所述多肽的方法，其包括在适合表达权利要求3中所述多肽的条件下培养权利要求20的宿主细胞。

23.分离的多肽，具有选自下组之序列：SEQ ID NO：39、SEQ IDNO：41和SEQ ID NO：44，或者其保守取代的衍生物，其中所述衍生物保持诱导对B组链球菌(BGS)特异性的免疫应答的能力。

24.具有序列SEQ ID NO：39的权利要求23的分离的多肽。

25.具有序列SEQ ID NO：44的权利要求23的分离的多肽。

26.能产生对选自下组的序列具有结合特异性的抗体的分离的多肽：SEQ ID NO：39、SEQ ID NO：41和SEQ ID NO：44，其中所述多肽保持诱导对B组链球菌(BGS)特异性的免疫应答的能力。

27.具有序列SEQ ID NO：39的权利要求26的分离的多肽。

28.具有序列SEQ ID NO：44的权利要求26的分离的多肽。

29.具有选自下组之氨基酸序列的分离的多肽：SEQ ID NO：39、SEQ ID NO：41和SEQ ID NO：44。

30.具有SEQ ID NO：39的氨基酸序列的权利要求29的分离的多肽。

31.具有SEQ ID NO：44的氨基酸序列的分离的多肽。

32.根据权利要求29-31任一项的分离的多肽，其中N-末端Met残基缺失。

33.根据权利要求29-30任一项的分离的多肽，其中分泌氨基酸序列缺失。

34.疫苗组合物，其包括权利要求23-31任一项的多肽和药学上可接受的载体，稀释剂或佐剂。

35.疫苗组合物，其包括根据权利要求32的一种多肽和药学可接受载体，稀释剂或佐剂。

36.疫苗组合物，其包括根据权利要求33的一种多肽和药学可接受载体，稀释剂或佐剂。

37.权利要求34的疫苗组合物在制备用于治疗性或预防性治疗对链球菌感染易感动物的链球菌感染的药物中的用途。

38.权利要求35的疫苗组合物在制备用于治疗性或预防性治疗对链球菌感染易感动物的链球菌感染的药物中的用途。

39.权利要求36的疫苗组合物在制备用于治疗性或预防性治疗对链球菌感染易感动物的链球菌感染的药物中的用途。

40.根据权利要求37-39任一项的用途，其中所述动物是牛。

41.根据权利要求37-39任一项的用途，其中所述动物是人。

42.根据权利要求37-39任一项的用途，其中所述链球菌感染选自A组链球菌和B组链球菌。

43.根据权利要求42的用途，其中所述链球菌感染是B组链球菌。

44.根据权利要求23-31任一项的一种多肽在制备用于治疗性或预防性治疗对链球菌感染易感动物的链球菌感染的疫苗的用途。

45.根据权利要求32的一种多肽在制备用于治疗性或预防性治疗对链球菌感染易感动物的链球菌感染的疫苗中的用途。

46.根据权利要求33的一种多肽在制备用于治疗或预防性治疗对链球菌感染易感动物的链球菌感染的疫苗中的用途。

47.权利要求23或26的分离多肽，其由在严格条件下与选自下组之序列杂交的多核苷酸编码：SEQ ID NO：37，SEQ ID NO：42和SEQIDNO：43。

48.权利要求23的分离多肽，其与选自下组之序列有至少95％的序列一致性：SEQ ID NO：39，SEQ ID NO：41和SEQ ID NO：44。