CN110603262A - 显示副粘病毒和/或肺炎病毒f蛋白的自组装蛋白纳米结构及其用途 - Google Patents

显示副粘病毒和/或肺炎病毒f蛋白的自组装蛋白纳米结构及其用途 Download PDF

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CN110603262A
CN110603262A CN201880023734.8A CN201880023734A CN110603262A CN 110603262 A CN110603262 A CN 110603262A CN 201880023734 A CN201880023734 A CN 201880023734A CN 110603262 A CN110603262 A CN 110603262A
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N·P·金
D·贝克
B·尼克森
L·J·斯图尔特
L·佩雷斯
A·兰扎韦基亚
J·马坎达力
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University of Washington
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Abstract

本文公开了纳米结构及其用途，其中该纳米结构包括(a)多个第一组件，每个第一组件包含多个相同的第一多肽；(b)多个第二组件，每个第二组件包含多个相同的第二多肽，其中所述第二多肽不同于所述第一多肽；其中多个第一组件与多个第二组件非共价地相互作用以形成纳米结构；并且其中所述纳米结构在所述纳米结构的外部上显示一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段的多个拷贝。

Description

显示副粘病毒和/或肺炎病毒F蛋白的自组装蛋白纳米结构及 其用途
交叉引用
本申请要求于2017年4月4日提交的美国临时专利申请序列号62/481331的优先权，其通过引用整体并入本文。
背景技术
蛋白的分子自组装和共组装成高度有序、对称的超分子复合物是一种在原子尺度上构图物质的优雅而强大的手段。近年来，自组装生物材料(特别是由核酸组成的自组装生物材料)的开发已经取得了进展。DNA已用于创建例如纳米级形状和图案、分子容器和三维宏观晶体。设计自组装蛋白的方法进展较慢，但蛋白的功能和物理特性使其成为开发高级功能材料的组成部分而具有吸引力。
发明内容
本发明的一方面，提供了纳米结构，其包含：
(a)多个第一组件，每个第一组件包含多个相同的第一多肽；
(b)多个第二组件，每个第二组件包含多个相同的第二多肽，其中所述第二多肽不同于所述第一多肽；
其中，多个第一组件与多个第二组件非共价地相互作用以形成纳米结构；并且
其中，所述纳米结构在所述纳米结构的外部上显示一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段的多个拷贝。
在一个实施方式中，(a)所述第一多肽包含沿其全长与选自由SEQ ID NO：1-51组成的组中的多肽的氨基酸序列具有至少70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽；并且
(b)所述第二多肽包含沿其全长与选自由SEQ ID NO：1-51组成的组中的多肽的氨基酸序列具有至少70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
在另一个实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段包含沿其全长与选自由SEQ ID NO：53、61-68和101组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
在各种实施方式中：
(a)所述第一多肽包含沿其全长与氨基酸序列T33-31A(SEQ ID NO：51)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列T33-09B/T33-31B(SEQ ID NO：44)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽；
(b)所述第一多肽包含沿其全长与氨基酸序列T33-15B(SEQ ID NO：46)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列T33-15A(SEQ ID NO：45)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽；
(c)所述第一多肽沿其全长与选自由I53-50A(SEQ ID NO：7)、I53-50A.1(SEQ IDNO：29)、I53-50A.1NegT2(SEQ ID NO：30)和I53-50A.1PosT1(SEQ ID NO：31)组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性，并且所述第二多肽沿其全长与选自由I53-50B(SEQ IDNO：8)、I53-50B.1(SEQ ID NO：32)、I53-50B.1NegT2(SEQ ID NO：33)和I53-50B.4PosT1(SEQ ID NO：34)组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性；或者
(d)所述第一多肽包含沿其全长与氨基酸序列I32-28A(SEQ ID NO：21)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列I32-28B(SEQ ID NO：22)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
在一个实施方式中，将一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段表达为与所述第一多肽的融合蛋白。在一个这样的实施方式中，多个第一组件各自包含相同的所述第一多肽；在另一个这样的实施方式中，多个第一组件总共包含两种或更多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段。在另一个实施方式中，仅所述第一多肽的子集包含具有F蛋白或其抗原片段的融合蛋白。在另一个实施方式中，每个第一组件包含所述第一多肽的同源三聚体。
在另一个实施方式中，所述融合蛋白包含位于所述第一多肽与副粘病毒和/或肺炎病毒F蛋白或其抗原片段之间的氨基酸接头。在一个这样的实施方式中，所述融合蛋白包含位于所述第一多肽与副粘病毒F蛋白或其抗原片段之间的氨基酸接头。
在一个实施方式中，氨基酸接头序列包含一个或多个三聚化结构域；在另一个实施方式中，氨基酸接头序列包含Gly-Ser接头。
在各种实施方式中，所述第一多肽包含或者由沿其全长与选自由DS-Cav1-折叠子-T33-31A(SEQ ID NO：69)、DS-Cav1-T33-31A(SEQ ID NO：70)、DS-Cav1-折叠子-T33-15B(SEQ ID NO：71)、DS-Cav1-T33-15B(SEQ ID NO：72)、DS-Cav1-折叠子-I53-50A(SEQ IDNO：73)、DS-Cav1-I53-50A(SEQ ID NO：74)和DS-Cav1-I32-28A(SEQ ID NO：75)组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽组成。
在其它实施方式中，
(a)当每个第一多肽沿其全长与氨基酸序列DS-Cav1-折叠子-T33-31A(SEQ IDNO：69)或DS-Cav1-T33-31A(SEQ ID NO：70)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性时，每个第二多肽沿其全长与氨基酸序列T33-31B(SEQ ID NO：44)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性；
(b)当每个第一多肽沿其全长与氨基酸序列DS-Cav1-折叠子-T33-15B(SEQ IDNO：71)或DS-Cav1-T33-15B(SEQ ID NO：72)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性时，每个第二多肽沿其全长与氨基酸序列T33-15A(SEQ ID NO：45)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性；
(c)当每个第一多肽沿其全长与氨基酸序列DS-Cav1-折叠子-I53-50A(SEQ IDNO：73)或DS-Cav1-I53-50A(SEQ ID NO：74)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性时，每个第二多肽沿其全长与选自由I53-50B(SEQ ID NO：8)、I53-50B.1(SEQ ID NO：32)、I53-50B.1NegT2(SEQ ID NO：33)或I53-50B.4PosT1(SEQ ID NO：34)组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性；或者
(d)当每个第一多肽沿其全长与氨基酸序列DS-Cav1-I32-28A(SEQ ID NO：75)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性时，每个第二多肽沿其全长与氨基酸序列I32-28B具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性。
在一个实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段包含沿其全长与氨基酸序列DS-Cav1(SEQ ID NO：53)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。在一个这样的实施方式中，每个第一多肽包含通过氨基酸接头将沿其全长与氨基酸序列DS-Cav1具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽与沿其全长与氨基酸序列SEQ ID NO：7(I53-50A)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽连接的融合多肽。在另一个实施方式中，所述氨基酸接头包含Gly-Ser接头。在另一个实施方式中，每个融合蛋白包含沿其全长与选自由SEQ ID NO：69-100组成的组中的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。在一个特定实施方式中，每个融合蛋白包含沿其全长与氨基酸序列SEQ ID NO：76(F10)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。在其它实施方式中，每个第二个多肽包含沿其全长与选自由I53-50B(SEQ IDNO：8)、I53-50B.1(SEQ ID NO：32)、I53-50B.1NegT2(SEQ ID NO：33)或I53-50B.4PosT1(SEQ ID NO：34)组成的组中的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。在一个特定实施方式中，每个第二个多肽包含沿其全长与氨基酸序列I53-50B.4PosT1(SEQ ID NO：34)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
在其它方面，提供了表达第一多肽融合体的重组表达核酸，包含与启动子连接的重组核酸的重组表达载体以及包含重组表达载体的重组宿主细胞。
还提供了包含本文所公开的任何实施方式或实施方式组合的纳米结构和药学上可接受的载体的免疫原性组合物。在一个实施方式中，该免疫原性组合物可以进一步包含佐剂。
在其它方面，提供了用于在受试者中产生对RSV F蛋白免疫应答或用于治疗或限制受试者RSV感染的方法，该方法包括向有此需要的受试者施用有效量的本文所公开实施方式或实施方式组合的纳米结构或免疫原性组合物以产生免疫应答或治疗或预防受试者的RSV感染。
还提供了组装本文所公开的任何实施方式或实施方式组合的纳米结构的工艺，其包括在水性条件下将两种或更多种纳米结构组分混合以驱动所需纳米结构的自发组装。
附图说明
当结合附图时，通过参考下面的详细描述，随着对本发明的前述方面和许多附带优点的更好理解，它们将变得更容易地理解。
图1显示了通过体外组装产生带有抗原的纳米结构的示意图。单独地表达和纯化给定纳米结构的两个组分或组成部分，这允许通过在体外混合纯化的组分来启动纳米结构的组装，此过程称为体外组装。在一些实施方式中，可以在不同的表达宿主(例如人HEK293F细胞或细菌大肠杆菌细胞)中表达纳米结构的两组分。该图示意性地描绘了通过体外组装在HEK293F细胞中产生的抗原-纳米结构三聚体融合蛋白和在大肠杆菌中产生的纳米结构五聚体蛋白来组装带有20个三聚体抗原(60个抗原亚基)的120个亚基纳米结构。
图2显示了说明在组织培养上清液中检测到分泌的DS-Cav1、DS-Cav1-折叠子-T33-31A和DS-Cav1-T33-31A融合蛋白的图。对表达DS-Cav1(上)、DS-Cav-1-折叠子-T33-31A/T33-31B(左下)和DS-Cav-1-T33-31A/T33-31B(右下)的细胞的组织培养上清液进行ELISA测定。结合RSV F的四种不同单克隆抗体用于评估上清液中DS-Cav1或DS-Cav1融合蛋白的存在。该结果证实了包含折叠良好的RSV F抗原的蛋白的分泌。
图3显示了DS-Cav1-I53-50A的尺寸排阻色谱。将通过固定的金属亲和色谱从组织培养上清液中纯化的蛋白施加于SuperoseTM 6 10/300GL尺寸排阻色谱柱。将蛋白洗脱为单个单分散种类。
图4显示了体外组装的DS-Cav1-I53-50纳米结构的尺寸排阻色谱。将纯化的DS-Cav1-I53-50A和I53-50B.4PT1蛋白以大约1：1的摩尔比混合，在4℃下温育过夜，然后施加于Sephacryl S-500 16/60HR尺寸排阻色谱柱。将组装的纳米结构以约65mL的单个单分散峰洗脱，而将多余的DS-Cav1-I53-50A三聚体组分以约90mL洗脱。
图5显示了在体外组装的DS-Cav1-I53-50纳米结构的负染色电子显微照片和二维类别平均值。通过尺寸排阻色谱纯化的体外组装的DS-Cav1-I53-50纳米结构通过负染色电子显微镜成像(上)。平均许多纳米结构会产生二维类别平均值(底部)，表明了该纳米结构的I53-50部分是高度有序且一致的，而所显示抗原的精确三维位置由于DS-Cav1-I53-50A融合蛋白的DS-Cav1和I53-50A结构域之间的接头的柔性性质而略有不同。
图6显示了描绘DS-Cav1-I53-50纳米结构的抗原性的一系列图。使用四种RSV F特异性单克隆抗体(包括融合前特异性抗体MPE8，D25和RSD5)通过ELISA(A)分析纯化的DS-Cav1-I53-50纳米结构，表明了当在DS-Cav1-I53-50纳米结构上多价态地显示时，DS-Cav1抗原正确折叠并保持在融合前状态。通过使用多种RSV F特异性抗体(B-C)进行表面等离振子共振测量证实了该发现，当与三聚体DS-Cav1相比时，这进一步暗示了DS-Cav1的多价态显示会导致亲和力效应，从而降低抗体的解离速率。
图7是描绘来自用DS-Cav1-I53-50纳米结构免疫的小鼠的DS-Cav1特异性血清抗体滴度的图。用缺乏额外抗原的I53-50纳米结构、三聚体DS-Cav1或带有DS-Cav1抗原的I53-50纳米结构以33％、66％或100％的价态免疫小鼠组。通过ELISA在涂覆有DS-Cav1的平板上测定DS-Cav1特异性血清抗体滴度。将每只鼠的血清抗体滴度绘制为圆圈，将每组内的几何平均值绘制为水平线。
图8是描绘通过用DS-Cav1-I53-50纳米结构免疫而引发的血清中和活性的图。用缺乏额外抗原的I53-50纳米结构、三聚体DS-Cav1或带有DS-Cav1抗原的I53-50纳米结构以33％、66％或100％的价态免疫小鼠组。将每只鼠的中和滴度绘制为圆圈，将每组内的几何平均值绘制为水平线。
图9是描绘通过用DS-Cav1-折叠子I53-50纳米结构免疫而引发的灵长类动物免疫系统的免疫原性的图。在第0周和第4周向恒河猕猴注射以100％价态DS-Cav1显示的游离DS-Cav1三聚体或DS-Cav1-折叠子-I53-50纳米结构。在这两种情况下，DS-Cav1抗原的剂量均为50μg，并用MF59类角鲨烯基水包油乳液佐剂SWE配制免疫原。评估在第6周和第16周时从动物获得的血清的抗DS-Cav1抗体滴度(A)和RSV中和抗体滴度(B)。
图10是描绘当融合至I53-50A时和/或进一步组装成二十面体纳米结构时的DS-Cav1的物理稳定性的图。将含有等价浓度DS-Cav1的三聚体DS-Cav1、三聚体DS-Cav1-I53-50A和DS-Cav1-I53-50纳米结构的样品分为四个等分试样，并在20、50、70或80℃下温育1小时。冷却至室温后，通过表面等离子体共振(SPR)测定D25结合。
图11是描绘纳米结构的物理稳定性的图。使用通过固有的色氨酸荧光监测盐酸胍(GdnHCl)中的化学变性作为第二种独立于抗体的技术来评估三聚体DS-Cav1(A-B)、DS-Cav1-折叠子-I53-50A(C-D)、DS-Cav1-折叠子-I53-50(E-F)、I53-50(G-H)和I53-50A(I-J)的物理稳定性。当与I53-50A纳米结构组分基因融合时，该数据表明了DS-Cav1抗原具有优越的物理稳定性。
具体实施方式
引用的所有参考文献均通过引用整体并入本文。在本申请中，除非另有说明，否则所利用的技术可以在以下几个众所周知的参考文献中找到，例如：Molecular Cloning:ALaboratory Manual(Sambrook等人,1989,Cold Spring Harbor Laboratory Press)，GeneExpression Technology(Methods in Enzymology,Vol.185,由D.Goeddel编辑,1991.Academic Press,San Diego,CA)，“Guide to Protein Purification”in Methodsin Enzymology(M.P.Deutshcer编辑,(1990)Academic Press,Inc.)；PCR Protocols:AGuide to Methods and Applications(Innis,等人1990.Academic Press,San Diego,CA),Culture of Animal Cells:A Manual of Basic Technique,第二次编辑.(R.I.Freshney.1987.Liss,Inc.New York,NY)，Gene Transfer and ExpressionProtocols,pp.109-128,编辑E.J.Murray,The Humana Press Inc.,Clifton,N.J.)和theAmbion 1998Catalog(Ambion,Austin,TX)。
如本文所用，除非上下文另有明确说明，否则单数形式“一个”，“一种”和“该”包括复数指示物。除非另有明确陈述，否则本文所用的“和”可与“或”互换使用。
如本文所用，氨基酸残基缩写如下：丙氨酸(Ala；A)、天冬酰胺(Asn；N)、天冬氨酸(Asp；D)、精氨酸(Arg；R)、半胱氨酸(Cys；C)、谷氨酸(Glu；E)、谷氨酰胺(Gln；Q)、甘氨酸(Gly；G)、组氨酸(His；H)、异亮氨酸(Ile；I)、亮氨酸(Leu；L)、赖氨酸(Lys；K)、甲硫氨酸(Met；M)、苯丙氨酸(Phe；F)、脯氨酸(Pro；P)、丝氨酸(Ser；S)、苏氨酸(Thr；T)、色氨酸(Trp；W)、酪氨酸(Tyr；Y)和缬氨酸(Val；V)。
如本文所用，“约”是指所述参数的+/-5％。
除非上下文另有明确说明，否则可以组合使用本发明的任何方面的所有实施方式。
除非上下文另有明确要求，否则在整个说明书和权利要求书中，“包括”、“包含”等词语应理解为与排他性或穷举性相反的包括性含义；也就是说，为“包括但不限于”的含义。使用单数或复数的词语也分别包括复数和单数。另外，当在本申请中使用时，词语“本文”，“上文”和“下文”以及类似含义的词语应整体上指本申请，而不是本申请的任何特定部分。
本公开实施方式的描述并非旨在穷举或将本公开限制为所公开的精确形式。尽管出于说明性目的本文描述了本公开的特定实施方式和22示例，但是如相关领域的技术人员将认识到的，在本公开范围内可能进行各种等价修饰。
在第一方面，本公开提供了纳米结构，其包含：
(a)多个第一组件，每个第一组件包含多个相同的第一多肽；
(b)多个第二组件，每个第二组件包含多个相同的第二多肽，其中所述第二多肽不同于所述第一多肽；
其中，多个第一组件与多个第二组件非共价地相互作用以形成纳米结构；并且
其中，所述纳米结构在所述纳米结构的外部上显示一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段的多个拷贝。
本文公开了自组装多肽纳米结构，其在纳米结构外部上多价地显示副粘病毒和/或肺炎病毒F蛋白。第一多肽和第二多肽对的多个拷贝能够自组装以形成纳米结构，例如二十面体纳米结构。纳米结构包括对称重复、非天然、非共价多肽-多肽界面，该界面将第一组件和第二组件定向为纳米结构，例如具有二十面体对称性的纳米结构。
本发明的纳米结构是合成的，因为它们不是天然存在的。第一多肽和第二多肽是非天然存在的蛋白，其可以通过任何合适的手段产生，其包括重组产生或化学合成。多个第一多肽的每个成员彼此相同(尽管当第一多肽作为与一个或多个副粘病毒和/或肺炎病毒F蛋白或其抗原片段的融合多肽存在时，F蛋白或其抗原片段可以因第一多肽不同而不同)，并且多个第二多肽的每个成员彼此相同。第一蛋白和第二蛋白不同。对于第一多肽和第二多肽没有特定的一级氨基酸序列要求。美国公开的专利申请20160122392和公开的PCT申请WO2014/124301描述了设计合成纳米结构的方法，其中所述纳米结构不依赖于第一多肽和第二多肽特定的一级氨基酸序列。
多个(2、3、4、5、6或更多个)第一多肽自组装以形成第一组件，并且多个(2、3、4、5、6或更多个)第二多肽自组装以形成第二组件。然后，多个第一组件和第二组件通过设计的界面非共价地自组装以产生纳米结构。
第一组件中的第一多肽的数量可以与第二组件中的第二多肽的数量相同或不同。在一个示例性的实施方式中，第一组件包含第一多肽的三聚体，且第二组件包含第二多肽的二聚体。在另一个示例性的实施方式中，第一组件包含第一多肽的三聚体，且第二组件包含第二多肽的三聚体。在另一个示例性的实施方式中，第一组件包含第一多肽的三聚体，且第二组件包含第二多肽的五聚体。
为了所得纳米结构的给定目的，第一多肽和第二多肽可以具有任何合适的长度。在一个实施方式中，所述第一多肽和第二多肽的长度通常在30-250个氨基酸之间；所述第一多肽和第二多肽的长度可以相同或不同。在各种其它实施方式中，所述第一多肽和第二多肽的长度在30-225、30-200、30-175、50-250、50-225、50-200、50-175、75-250、75-225、75-200、75-175、100-250、100-225、100-200、100-175、125-250、125-225、125-200、125-175、150-250、150-225、150-200和150-175个氨基酸之间。
为了使其具有成对自组装以形成纳米结构(例如二十面体纳米结构)的能力而设计SEQ ID NO：1-51的分离多肽。该设计涉及为多肽对的每个成员设计合适的界面残基，该多肽对可以被组装以形成纳米结构。如此形成的纳米结构形成包括对称重复、非天然、非共价多肽-多肽界面，该界面将第一组件和第二组件定向为纳米结构，例如具有二十面体对称性的纳米结构。因此，在一个实施方式中，第一多肽和第二多肽选自由SEQ ID NO：1-51组成的组。在每种情况下，N末端甲硫氨酸残基是可选的。
表1
I53-40A属(SEQ ID NO：35)
(M)TKKVGIVDTTFARVDMASAAILTLKMESPNIKIIRKTVPGIKDLPVACKKLLEEEGCDIVMALGMPGK(A/K)EKDKVCAHEASLGLMLAQLMTNKHIIEVFVHEDEAKDDAELKILAARRAIEHALNVYYLLFKPEYLTRMAGKGLRQGFEDAGPARE
I53-40B属(SEQ ID NO：36)
(M)
(S/D)(T/D)INNQLK(A/R)LKVIPVIAIDNAEDIIPLGKVLAENGLPAAEITFRSSAAVKAIMLLRSAQPEMLIGAGTILNGVQALAAKEAGA(T/D)FVVSPGFNPNTVRACQIIGIDIVPGVNNPSTVE(A/Q)ALEMGLTTLKFFPAEASGGISMVKSLVGPYGDIRLMPTGGITP(S/D)NIDNYLAIPQVLACGGTWMVDKKLV(T/R)NGEWDEIARLTREIVEQVNP
I53-47A属(SEQ ID NO：37)
(M)PIFTLNTNIKA(T/D)DVPSDFLSLTSRLVGLILS(K/E)PGSYVAVHINTDQQLSFGGSTNPAAFGTLMSIGGIEP(S/D)KN(R/E)DHSAVLFDHLNAMLGIPKNRMYIHFV(N/D)L(N/D)GDDVGWNGTTF
I53-47B属(SEQ ID NO：38)
(M)NQHSHKD(Y/H)ETVRIAVVRARWHADIVDACVEAFEIAMAAIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVV(N/D)GGIY(R/D)HEFVASAVIDGMMNVQL(S/D)TGVPVLSAVLTPH(R/E)Y(R/E)DS(A/D)E(H/D)H(R/E)FFAAHFAVKGVEAARACIEIL(A/N)AREKIAA
I53-50A属(SEQ ID NO：39)
(M)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGH(T/D)ILKLFPGEVVGP(Q/E)FV(K/E)AMKGPFPNVKFVPTGGV(N/D)LD(N/D)VC(E/K)WF(K/D)AGVLAVGVG(S/K/D)ALV(K/E)G(T/D/K)PDEVRE(K/D)AK(A/E/K)FV(E/K)(K/E)IRGCTE
I53-50B属(SEQ ID NO：40)
(M)NQHSHKD(Y/H)ETVRIAVVRARWHAEIVDACVSAFEAAM(A/R)DIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVV(N/D)GGIY(R/D)HEFVASAVI(D/N)GMMNVQL(S/D/N)TGVPVLSAVLTPH(R/E/N)Y(R/D/E)(D/K)S(D/K)A(H/D)TLLFLALFAVKGMEAARACVEILAAREKIAA
T32-28A(SEQ ID NO：41)
(M)GEVPIGDPKELNGMEIAAVYLQPIEMEPRGIDLAASLADIHLEADIHALKNNPNGFPEGFWMPYLTIAYALANADTGAIKTGTLMPMVADDGPHYGANIAMEKDKKGGFGVGTYALTFLISNPEKQGFGRHVDEETGVGKWFEPFVVTYFFKYTGTPK
T32-28B(SEQ ID NO：42)
(M)SQAIGILELTSIAKGMELGDAMLKSANVDLLVSKTISPGKFLLMLGGDIGAIQQAIETGTSQAGEMLVDSLVLANIHPSVLPAISGLNSVDKRQAVGIVETWSVAACISAADLAVKGSNVTLVRVHMAFGIGGKCYMVVAGDVLDVAAAVATASLAAGAKGLLVYASIIPRPHEAMWRQMVEG
T33-09A(SEQ ID NO：43)
(M)EEVVLITVPSALVAVKIAHALVEERLAACVNIVPGLTSIYRWQGSVVSDHELLLLVKTTTHAFPKLKERVKALHPYTVPEIVALPIAEGNREYLDWLRENTG
T33-09B(SEQ ID NO：44)
(M)VRGIRGAITVEEDTPAAILAATIELLLKMLEANGIQSYEELAAVIFTVTEDLTSAFPAEAARLIGMHRVPLLSAREVPVPGSLPRVIRVLALWNTDTPQDRVRHVYLNEAVRLRPDLESAQ
T33-15A(SEQ ID NO：45)
(M)SKAKIGIVTVSDRASAGITADISGKAIILALNLYLTSEWEPIYQVIPDEQDVIETTLIKMADEQDCCLIVTTGGTGPAKRDVTPEATEAVCDRMMPGFGELMRAESLKEVPTAILSRQTAGLRGDSLIVNLPGDPASISDCLLAVFPAIPYCIDLMEGPYLECNEAMIKPFRPKAK
T33-15B(SEQ ID NO：46)
(M)VRGIRGAITVNSDTPTSIIIATILLLEKMLEANGIQSYEELAAVIFTVTEDLTSAFPAEAARQIGMHRVPLLSAREVPVPGSLPRVIRVLALWNTDTPQDRVRHVYLSEAVRLRPDLESAQ
T33-21A(SEQ ID NO：47)
(M)RITTKVGDKGSTRLFGGEEVWKDSPIIEANGTLDELTSFIGEAKHYVDEEMKGILEEIQNDIYKIMGEIGSKGKIEGISEERIAWLLKLILRYMEMVNLKSFVLPGGTLESAKLDVCRTIARRALRKVLTVTREFGIGAEAAAYLLALSDLLFLLARVIEIEKNKLKEVRS
T33-21B(SEQ ID NO：48)
(M)PHLVIEATANLRLETSPGELLEQANKALFASGQFGEADIKSRFVTLEAYRQGTAAVERAYLHACLSILDGRDIATRTLLGASLCAVLAEAVAGGGEEGVQVSVEVREMERLSYAKRVVARQR
T33-28A(SEQ ID NO：49)
(M)ESVNTSFLSPSLVTIRDFDNGQFAVLRIGRTGFPADKGDIDLCLDKMIGVRAAQIFLGDDTEDGFKGPHIRIRCVDIDDKHTYNAMVYVDLIVGTGASEVERETAEEEAKLALRVALQVDIADEHSCVTQFEMKLREELLSSDSFHPDKDEYYKDFL
T33-28B(SEQ ID NO：50)
(M)PVIQTFVSTPLDHHKRLLLAIIYRIVTRVVLGKPEDLVMMTFHDSTPMHFFGSTDPVACVRVEALGGYGPSEPEKVTSIVTAAITAVCGIVADRIFVLYFSPLHCGWNGTNF
T33-31A(SEQ ID NO：51)
(M)EEVVLITVPSALVAVKIAHALVEERLAACVNIVPGLTSIYREEGSVVSDHELLLLVKTTTDAFPKLKERVKELHPYEVPEIVALPIAEGNREYLDWLRENTG
表1提供了第一多肽和第二多肽的氨基酸序列。表1的右栏标识了每个示例性多肽中的残基编号，这些残基编号被鉴定为存在于所得组装纳米结构的界面上(即：“经鉴定的界面残基”)。可以看出，SEQ ID NO：1-34的示例性多肽的界面残基的数量范围为4-13。在各种实施方式中，第一多肽和第二多肽包含沿其长度与选自由SEQ ID NO：1-34组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％同一性且在至少1、2、3、4、5、6、7、8、9、10、11、12或13个经鉴定的界面位置(依赖于给定多肽的界面残基数量)具有同一性的氨基酸序列。在其它实施方式中，第一多肽和第二多肽包含沿其长度与选自由SEQ ID NO：1-51组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％同一性且在至少20％、25％、33％、40％、50％、60％、70％、75％、80％、90％或100％经鉴定的界面位置具有同一性的氨基酸序列。
通常，与蛋白一样，期望多肽耐受设计序列中的某些变异，而不会破坏随后组装成纳米结构：特别是当这种变异包含保守的氨基酸取代时。在此所用的，“保守的氨基酸取代”是指：疏水性氨基酸(Ala、Cys、Gly、Pro、Met、See、Sme、Val、Ile、Leu)只能被其它疏水性氨基酸取代；具有大侧链的疏水性氨基酸(Phe、Tyr、Trp)只能被其它具有大侧链的疏水性氨基酸取代；具有侧链带正电荷的氨基酸(Arg、His、Lys)只能被其它具有侧链带正电荷的氨基酸取代；具有侧链带负电荷的氨基酸(Asp、Glu)只能被其它具有侧链带负电荷的氨基酸取代；具有极性侧链不带电荷的氨基酸(Ser、Thr、Asn、Gln)只能被其它具有极性侧链不带电荷的氨基酸取代。
表2列出了由SEQ ID NO：1-34表示的本发明的每个示例性多肽的表面氨基酸残基数。因此，在各种实施方式中，可以修饰本发明的多肽的这些表面残基中的1或多个(至少1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50或更多个)。括号中的残基是可选的。
表2
在本发明的纳米结构的各种实施方式中，第一多肽和第二多肽包含具有选自以下对或其修饰形式的氨基酸序列的多肽(即：包含沿其长度与以下SEQ ID No表示的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性和/或在至少一个经鉴定的界面位置具有同一性的氨基酸序列的如本发明的多肽所公开的允许的修饰：分离的多肽)：
SEQ ID NO：1和SEQ ID NO：2(I53-34A和I53-34B)；
SEQ ID NO：3和SEQ ID NO：4(I53-40A和I53-40B)；
SEQ ID NO：3和SEQ ID NO：24(I53-40A和I53-40B.1)；
SEQ ID NO：23和SEQ ID NO：4(I53-40A.1和I53-40B)；
SEQ ID NO：35和SEQ ID NO：36(I53-40A属和I53-40B属)；
SEQ ID NO：5和SEQ ID NO：6(I53-47A和I53-47B)；
SEQ ID NO：5和SEQ ID NO：27(I53-47A和I53-47B.1)；
SEQ ID NO：5和SEQ ID NO：28(I53-47A和I53-47B.1NegT2)；
SEQ ID NO：25和SEQ ID NO：6(I53-47A.1和I53-47B)；
SEQ ID NO：25和SEQ ID NO：27(I53-47A.1和I53-47B.1)；
SEQ ID NO：25和SEQ ID NO：28(I53-47A.1和I53-47B.1NegT2)；
SEQ ID NO：26和SEQ ID NO：6(I53-47A.1NegT2和I53-47B)；
SEQ ID NO：26和SEQ ID NO：27(I53-47A.1NegT2和I53-47B.1)；
SEQ ID NO：26和SEQ ID NO：28(I53-47A.1NegT2和I53-47B.1NegT2)；
SEQ ID NO：37和SEQ ID NO：38(I53-47A属和I53-47B属)；
SEQ ID NO：7和SEQ ID NO：8(I53-50A和I53-50B)；
SEQ ID NO：7和SEQ ID NO：32(I53-50A和I53-50B.1)；
SEQ ID NO：7和SEQ ID NO：33(I53-50A和I53-50B.1NegT2)；
SEQ ID NO：7和SEQ ID NO：34(I53-50A和I53-50B.4PosT1)；
SEQ ID NO：29和SEQ ID NO：8(I53-50A.1和I53-50B)；
SEQ ID NO：29和SEQ ID NO：32(I53-50A.1和I53-50B.1)；
SEQ ID NO：29和SEQ ID NO：33(I53-50A.1和I53-50B.1NegT2)；
SEQ ID NO：29和SEQ ID NO：34(I53-50A.1和I53-50B.4PosT1)；
SEQ ID NO：30和SEQ ID NO：8(I53-50A.1NegT2和I53-50B)；
SEQ ID NO：30和SEQ ID NO：32(I53-50A.1NegT2和I53-50B.1)；
SEQ ID NO：30和SEQ ID NO：33(I53-50A.1NegT2和I53-50B.1NegT2)；
SEQ ID NO：30和SEQ ID NO：34(I53-50A.1NegT2和I53-50B.4PosT1)；
SEQ ID NO：31和SEQ ID NO：8(I53-50A.1PosT1和I53-50B)；
SEQ ID NO：31和SEQ ID NO：32(I53-50A.1PosT1和I53-50B.1)；
SEQ ID NO：31和SEQ ID NO：33(I53-50A.1PosT1和I53-50B.1NegT2)；
SEQ ID NO：31和SEQ ID NO：34(I53-50A.1PosT1和I53-50B.4PosT1)；
SEQ ID NO：39和SEQ ID NO：40(I53-50A属和I53-50B属)；
SEQ ID NO：9和SEQ ID NO：10(I53-51A和I53-51B)；
SEQ ID NO：11和SEQ ID NO：12(I52-03A和I52-03B)；
SEQ ID NO：13和SEQ ID NO：14(I52-32A和I52-32B)；
SEQ ID NO：15和SEQ ID NO：16(I52-33A和I52-33B)
SEQ ID NO：17和SEQ ID NO：18(I32-06A和I32-06B)；
SEQ ID NO：19和SEQ ID NO：20(I32-19A和I32-19B)；
SEQ ID NO：21和SEQ ID NO：22(I32-28A和I32-28B)；
SEQ ID NO：23和SEQ ID NO：24(I53-40A.1和I53-40B.1)；
SEQ ID NO：41和SEQ ID NO：42(T32-28A和T32-28B)；
SEQ ID NO：43和SEQ ID NO：44(T33-09A和T33-09B)；
SEQ ID NO：45和SEQ ID NO：46(T33-15A和T33-15B)；
SEQ ID NO：47和SEQ ID NO：48(T33-21A和T33-21B)；
SEQ ID NO：49和SEQ ID NO：50(T33-28A和T32-28B)；和
SEQ ID NO：51和SEQ ID NO：44(T33-31A和T33-09B(也称为T33-31B))
在一个实施方式中，将一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段表达为与所述第一多肽和/或第二多肽的融合蛋白。在这些实施方式中，只要这种构型可以促进一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段在纳米结构的外部上呈现，则优选在融合蛋白的N末端存在一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段。对于副粘病毒和/或肺炎病毒F蛋白在融合蛋白N末端存在的优选源自副粘病毒和/或肺炎病毒F蛋白的C末端位于F蛋白三聚体的一个极端(“底部”)；通过在此时定位基因融合体，大多数F蛋白结构将在纳米结构外部得以显示和可使用。在另一个实施方式中，所述纳米结构包含含有至少两个结构域-副粘病毒和/或肺炎病毒F蛋白或其抗原片段和三聚体组件结构域-的融合蛋白的一个或多个拷贝(即：每个第一组件是第一多肽的三聚体)和第二低聚部分的一个或多个拷贝(即：每个第二组件是第二多肽两个或多个拷贝的寡聚体)。在另一个实施方式中，可以修饰第一多肽和/或第二多肽以允许一个或多个副粘病毒和/或肺炎病毒F蛋白或其抗原片段与第一多肽和/或第二多肽共价连接。在一个非限制性示例中，可以修饰第一多肽和/或第二多肽，例如通过在限定的位置引入各种半胱氨酸残基来促进一个或多个副粘病毒和/或肺炎病毒F蛋白或其抗原片段的连接。
在其它实施方式中，通过任何合适的技术将一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段连接至第一多肽或第二多肽，该技术包括但不限于共价化学交联(通过任何合适的交联技术)和包括工程化的静电相互作用的非共价连接。
三聚体组件结构域
在包含三聚体副粘病毒和/或肺炎病毒F蛋白或其抗原片段的三聚体组件的一个实施方式中，将副粘病毒和/或肺炎病毒F蛋白或其抗原片段遗传融合至自组装成所述三聚体组件的第一多肽。三聚体组件包含蛋白-蛋白界面，该界面诱导第一多肽的三个拷贝自缔合以形成三聚体组成部分。第一多肽的每个拷贝进一步包含与第二组件结构域上的互补表面暴露界面相互作用的表面暴露界面。如King等人(Nature 510,103–108,2014)、Bale等人(Science 353,389–394,2016)以及专利公开WO2014124301A1和US20160122392A1中所述，三聚体组件结构域和第二组件结构域之间的互补蛋白-蛋白界面驱动将三聚体组件结构域和第二组件构域的多个拷贝组装成靶标纳米结构。在一些实施方式中，纳米结构的三聚体组件结构域的每个拷贝带有作为基因融合体的副粘病毒和/或肺炎病毒F蛋白或其抗原片段；这些纳米结构以完全价态显示F蛋白。在其它实施方式中，本发明的纳米结构包含带有作为基因融合体的副粘病毒和/或肺炎病毒F蛋白或其抗原片段的三聚体组件结构域以及一个或多个不带有作为基因融合体的F蛋白的三聚体组件结构域的一个或多个拷贝；这些纳米结构以部分价态显示F蛋白。三聚体组件结构域可以是形成三聚体并与第二组件结构域相互作用以驱动组装成靶标纳米结构的任何多肽序列。
在一个特定实施方式中，所述第一多肽包含沿其全长与氨基酸序列T33-31A(SEQID NO：51)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列T33-09B/T33-31B(SEQ ID NO：44)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽(括号中的残基是可选的)。
T33-31A(SEQ ID NO：51)
(M)EEVVLITVPSALVAVKIAHALVEERLAACVNIVPGLTSIYREEGSVVSDHELLLLVKTTTDAFPKLKERVKELHPYEVPEIVALPIAEGNREYLDWLRENTG
>T33-31B(SEQ ID NO：44)
(M)VRGIRGAITVEEDTPAAILAATIELLLKMLEANGIQSYEELAAVIFTVTEDLTSAFPAEAARLIGMHRVPLLSAREVPVPGSLPRVIRVLALWNTDTPQDRVRHVYLNEAVRLRPDLESAQ
在另一个特定实施方式中，所述第一多肽包含沿其全长与氨基酸序列T33-15A(SEQ ID NO：45)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列T33-15B(SEQ ID NO：46)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
在各种其它特定实施方式中，所述第一多肽包含沿其全长与选自由I53-50A(SEQID NO：7)、I53-50A.1(SEQ ID NO：29)、I53-50A.1NegT2(SEQ ID NO：30)和I53-50A.1PosT1(SEQ ID NO：31)组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与选自由I53-50B(SEQ ID NO：8)、I53-50B.1(SEQ ID NO：32)、I53-50B.1NegT2(SEQ ID NO：33)和I53-50B.4PosT1(SEQ ID NO：34)组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
在另一个特定实施方式中，所述第一多肽包含沿其全长与氨基酸序列I32-28A(SEQ ID NO：21)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列I32-28B(SEQ ID NO：22)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
本发明的纳米结构在纳米结构的外部上显示一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段的多个拷贝(即：2、3或更多个)。示例性副粘病毒和/或肺炎病毒包括但不限于呼吸道合胞病毒(RSV)和人偏肺炎病毒(hMPV)(C.L.Afonso等人,Taxonomy of theorder Mononegavirales:update 2016.Arch.Virol.161,2351–2360(2016))。
如本文所用，“在纳米结构的外部上”意指一种或多种副粘病毒和/或肺炎病毒F蛋白的抗原部分或其抗原片段必须易于与B细胞受体、抗体或抗体片段结合，并且不能掩埋在所述纳米结构内。
一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段可以包含任何合适的天然F蛋白、融合后抗原或融合前(preF)抗原或其能够诱导产生免疫应答的突变体，该免疫应答会产生与副粘病毒和/或肺炎病毒F蛋白结合的抗体。纳米结构可以显示一个以上的F蛋白；因此，在一些实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段包含1、2、3、4或更多个F蛋白或其抗原片段。在一个实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段可以为如专利公开号US 2016/0046675A1中所限定的。在一些实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段选自由如美国公开专利申请2016/0046675中所公开的SEQ ID NO：1-350、370-382、389-693、698-1026、1429-1442、1456-1468和1474-1478组成的组。在其它实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段可以为如专WO2012158613、US20160102123、US20140141037、WO2014079842、WO2014160463、US20140271699、EP2970393、WO2014174018、US20140271699、US20160176932、US20160122398、WO2017040387、WO2017109629、WO2017172890、WO2017207477、Krarup等人(2015)Nature Communications 6:8143和WO2017207480中所限定的。
在一个特定实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段包含沿其全长与如下所示的氨基酸序列DS-Cav1具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽(括号中的残基是可选的；注意到括号中的N末端残基是在分泌期间从蛋白上切割的-成熟的N末端开始于QNITEEF…(SEQ ID NO：52))。DS-Cav1包含融合(F)糖蛋白的融合前稳定化形式，其与融合后RSV F相比，在小鼠和猕猴中引发了针对呼吸道合胞病毒(RSV)改善的保护性应答(McLellan等人(2013)Science 342:592-8)。
DS-Cav1(SEQ ID NO：53)：
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)
在其它实施方式中，F蛋白可以包含沿其全长与选自以下的多肽具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽：
RSV F
sc9-10 DS-Cav1 A149C Y458C(SEQ ID NO：61)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAICSGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSRTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYCVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)
sc9-10 DS-Cav1 A149C Y458C S46G K465Q S215P E92D(SEQ ID NO：62)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLGALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTDLQLLMQSTPATGSGSAICSGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSRTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYCVNKQEGQSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)
SEQ ID NO：61-62代表第二代稳定化的DS-Cav1免疫原。注意到相对于DS-Cav1的突变，并且应该注意的是，本公开考虑了使用DS-Cav1突变体，其不同之处在于上文的SEQID NO：61或62中的单个所述氨基酸取代、或两个或多个所述氨基酸取代。在其它实施方式中，F蛋白可以包含以下中的一种或多种，其中每种都可以额外包括1、2或多个上文SEQ IDNO：61或62中所述的氨基酸取代：
RSV F SC-DM(N67I、S215P)(SEQ ID NO：63)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKKIKCNGTDAKIKLIKQELDKYKNAVTELQLLMQSTPATNNQARGSGSGRSLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELLSAIGGYIPEAPRDGQAYVRKDGEWVLLSTFL)
SC-TM(N67I、S215P和E487Q)(SEQ ID NO：64)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKKIKCNGTDAKIKLIKQELDKYKNAVTELQLLMQSTPATNNQARGSGSGRSLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDQFDASISQVNEKINQSLAFIR(KSDELLSAIGGYIPEAPRDGQAYVRKDGEWVLLSTFL)
HMPV F蛋白、菌株CAN97-83(A2)(SEQ ID NO：65)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVATAAAVTAGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLATAVRELKDFVSKNLTRAINKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTAAGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTG
具有A113C、A339C、T160F、I177L的HMPVF(SEQ ID NO：66)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVCTAAAVTAGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRALNKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTACGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTG
具有A113C、A120C、A339C、T160F、I177L和Q426C的HMPV F(SEQ ID NO：67)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVCTAAAVTCGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRALNKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTACGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYCLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTG
HMPV F>AAK62968.2融合蛋白[人偏肺炎病毒](SEQ ID NO：101)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCADGPSLIKTELDLTKSALRELRTVSADQLAREEQIENPRQSRFVLGAIALGVATAAAVTAGVAIAKTIRLESEVTAIKNALKKTNEAVSTLGNGVRVLATAVRELKDFVSKNLTRAINKNKCDIADLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGFLIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTAAGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPVKFPEDQFNVALDQVFESIENSQALVDQSNRILSSAEKGNTG
115-BV(A185P)(SEQ ID NO：68)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCADGPSLIKTELDLTKSALRELRTVSADQLAREEQIENPRRRRFVLGAIALGVATAAAVTAGVAIAKTIRLESEVTAIKNALKKTNEAVSTLGNGVRVLATAVRELKDFVSKNLTRAINKNKCDIPDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSEKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTAAGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPVKFPEDQFNVALDQVFESIENSQALVDQSNRILSSAEKGNT(SGRENLYFQGGGGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGGIEGRHHHHHH)
在其它实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段可以包含沿其全长与选自由SEQ ID NO：53和61-64组成的组中的RSV F蛋白或其突变体具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，其中所述多肽包括一个或多个以下残基：67I、149C、458C、46G、465Q、215P、92D和487Q。
在其它实施方式中，一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段可以包含沿其全长与选自由SEQ ID NO：65-68和101组成的组中的MPV F蛋白或其突变体具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，其中所述多肽包括一个或多个以下残基：113C、120C、339C、160F、177L、185P和426C。
F蛋白与三聚体组件结构域之间的接头和几何要求
在本发明的纳米结构中，可以将F蛋白和三聚体组件结构域遗传融合，使得它们都存在于单个多肽中。优选地，F蛋白和三聚体组件结构域之间的连接允许F蛋白或其抗原片段被显示在本发明的纳米结构的外部上。这样，在没有任何F蛋白的情况下，与三聚体组件结构域的连接点应在由三聚体组件结构域和第二组件结构域形成的纳米结构的外部上。如本领域技术人员将理解的，多种多肽序列可以用于将副粘病毒和/或肺炎病毒F蛋白或其抗原片段和三聚体组件结构域连接。将这些多肽序列称为接头。可以使用任何合适的接头；不需要氨基酸序列作为适当的接头。除了使F蛋白或其抗原片段被显示在本发明的纳米结构的外部上外，不需要接头使F蛋白或其抗原片段对三聚体组件结构域施加刚性相对定向。在一些实施方式中，所述接头包括有助于稳定F蛋白的三聚体形式的额外三聚化结构域(例如T4纤维蛋白的折叠结构域)。
T4纤维蛋白折叠结构域(可选在接头区域)(SEQ ID NO：54)
GYIPEAPRDGQAYVRKDGEWVLLSTFL
在其它实施方式中，所述接头可以包含任何合适长度的Gly-Ser接头(即：由甘氨酸和丝氨酸残基组成的接头)。在各种实施方式中，Gly-Ser接头的长度可以是3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20或更多个氨基酸。在各种实施方式中，Gly-Ser接头可以包含或者由氨基酸序列GSGGSGSGSGGSGSG(SEQ ID NO：55)、GGSGGSGS(SEQ ID NO：56)或GSGGSGSG(SEQ ID NO：57)组成。
在其它实施方式中，当表达为与一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段的融合多肽时，所述接头可以包含可用来延伸第一个多肽的N末端螺旋的螺旋延伸结构域，使其位于纳米结构表面的外部。螺旋延伸可以与本文所述的其它接头组分结合存在，或者可以不存在。螺旋延伸可以具有任何合适的长度(即：7、8、9、10、11、12或更多个氨基酸)，并包含任何合适的一级氨基酸序列。在一个实施方式中，螺旋延伸可以包含或由氨基酸序列EKAAKAEEAAR(SEQ ID NO：58)组成。
因此，在各种非限制性实施方式中，其中F蛋白作为与第一多肽的融合蛋白存在并且使用了接头，其中F蛋白接头序列可以包含以下序列(在这些非限制性实施方式中，以DS-Cav1作为F蛋白示例)。括号中的残基是可选的，并且氨基酸序列MELLILKANAITTILTAVTFCFASG(SEQ ID NO：59)代表在加工期间被切割的N末端DS-Cav1信号肽：
DS-Cav1-折叠子(SEQ ID NO：60)：
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLGYIPEAPRDGQAYVRKDGEWVLLSTFL
在各种其它实施方式中，第一多肽包含或由与F蛋白融合的第一多肽的融合多肽组成，其中，该融合蛋白具有选自以下的序列(括号中的残基是可选的)：
DS-Cav1-折叠子-T33-31A(SEQ ID NO：69)
(MELLILKANVIATILTAVTFCFASS)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLGYIPEAPRDGQAYVRKDGEWVLLSTFLGGSMEEVVLITVPSALVAVKIAHALVEERLAACVNIVPGLTSIYREEGSVVSDHELLLLVKTTTDAFPKLKERVKELHPYEVPEIVALPIAEGNREYLDWLRENTG
DS-Cav1-T33-31A(SEQ ID NO：70)
(MELLILKANVIATILTAVTFCFASS)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLGGSMEEVVLITVPSALVAVKIAHALVEERLAACVNIVPGLTSIYREEGSVVSDHELLLLVKTTTDAFPKLKERVKELHPYEVPEIVALPIAEGNREYLDWLRENTG
DS-Cav1-折叠子-T33-15B(SEQ ID NO：71)
(MELLILKANVIATILTAVTFCFASS)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLGYIPEAPRDGQAYVRKDGEWVLLSTFLGGSMVRGIRGAITVNSDTPTSIIIATILLLEKMLEANGIQSYEELAAVIFTVTEDLTSAFPAEAARQIGMHRVPLLSAREVPVPGSLPRVIRVLALWNTDTPQDRVRHVYLSEAVRLRPDLESAQ
DS-Cav1-T33-15B(SEQ ID NO：72)
(MELLILKANVIATILTAVTFCFASS)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLGGSMVRGIRGAITVNSDTPTSIIIATILLLEKMLEANGIQSYEELAAVIFTVTEDLTSAFPAEAARQIGMHRVPLLSAREVPVPGSLPRVIRVLALWNTDTPQDRVRHVYLSEAVRLRPDLESAQ
DS-Cav1-折叠子-I53-50A(SEQ ID NO：73)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
DS-Cav1-I53-50A(SEQ ID NO：74)
(MELLILKANVIATILTAVTFCFASS)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
DS-Cav1-I32-28A(SEQ ID NO：75)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLGGSGGSGSDDARIAAIGDVDELNSQIGVLLAEPLPDDVRAALSAIQHDLFDLGGELCIPGHAAITEDHLLRLALWLVHYNGQLPPLEEFILPGGARGAALAHVCRTVCRRAERSIKALGASEPLNIAPAAYVNLLSDLLFVLARVLNRAAGGADVLWDRTRAH
DS-Cav1-8GS-HelExt-I53-50A(F10)(SEQ ID NO：76)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
DS-Cav1-折叠子-15GS-HelExt-I53-50A(F14)(SEQ ID NO：77)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGSGSGSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
HMPV F wt_CAN97-83菌株-I53-50A(SEQ ID NO：78)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVATAAAVTAGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLATAVRELKDFVSKNLTRAINKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTAAGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTGFIIVIILIAVLGSSMILVSIFIIIKKTKKPTGAPPELSGVTNNGFIPHSGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
HMPV F A113C_A339C_T160F_I177L-I53-50A(SEQ ID NO：79)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVCTAAAVTAGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRALNKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTACGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTGGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
HMPV F A113C_A339C_T160F_I177L_A120C，Q426C突变-I53-50A(SEQ ID NO：80)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVCTAAAVTCGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRALNKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTACGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYCLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTGGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
sc-DS2-I53-50A(SEQ ID NO：81)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSCIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYCVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
tc-DS2-I53-50A(SEQ ID NO：82)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSCIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYCVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
DS-Cav1-12GS-HelExt-I53-50A(F11)(SEQ ID NO：83)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGSGGSGSGSGGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
DS-Cav1-16GS-HelExt-I53-50A(F12)(SEQ ID NO：84)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGSGGSGSGSGGSGSGGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
DS-Cav1-折叠子-10GS-HelExt-I53-50A(F13)(SEQ ID NO：85)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGSGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
DS-Cav1-折叠子-20GS-HelExt-I53-50A(F15)(SEQ ID NO：86)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGGSGSGSGGSGSGGSSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
sc9-10 DS-Cav1 A149C Y458C-折叠子-I53-50A实施方式(SEQ ID NO：87)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAICSGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSRTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYCVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)GYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
sc9-10 DS-Cav1 A149C Y458C-I53-50A-F10实施方式(SEQ ID NO：88)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAICSGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSRTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYCVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)GSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
sc9-10 DS-Cav1 A149C Y458C S46G K465Q S215P E92D-折叠子-I53-50A实施方式(SEQ ID NO：89)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLGALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTDLQLLMQSTPATGSGSAICSGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSRTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYCVNKQEGQSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)GYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
sc9-10 DS-Cav1 A149C Y458C S46G K465Q S215P E92D-I53-50A-F10实施方式(SEQ ID NO：90)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLGALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTDLQLLMQSTPATGSGSAICSGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSRTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYCVNKQEGQSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)GSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
SC-DM(N67I，S215P)-折叠子-I53-50A实施方式(SEQ ID NO：91)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKKIKCNGTDAKIKLIKQELDKYKNAVTELQLLMQSTPATNNQARGSGSGRSLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)GYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
SC-DM(N67I，S215P)-I53-50A-F10实施方式(SEQ ID NO：92)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKKIKCNGTDAKIKLIKQELDKYKNAVTELQLLMQSTPATNNQARGSGSGRSLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL)GSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
SC-TM(N67I、S215P和E487Q)-折叠子-I53-50A实施方式(SEQ ID NO：93)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKKIKCNGTDAKIKLIKQELDKYKNAVTELQLLMQSTPATNNQARGSGSGRSLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDQFDASISQVNEKINQSLAFIR(KSDELL)GYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
SC-TM(N67I、S215P和E487Q)-I53-50A-F10实施方式(SEQ ID NO：94)
(MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKKIKCNGTDAKIKLIKQELDKYKNAVTELQLLMQSTPATNNQARGSGSGRSLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDQFDASISQVNEKINQSLAFIR(KSDELL)GSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
具有A113C、A339C、T160F、I177L-折叠子-I53-50A的HMPV-F实施方式(SEQ ID NO：95)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVCTAAAVTAGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRALNKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTACGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTGGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
具有A113C、A339C、T160F、I177L-I53-50AF10的HMPV-F实施方式(SEQ ID NO：96)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVCTAAAVTAGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRALNKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTACGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTGGSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
具有A113C、A120C、A339C、T160F、I177L和Q426C-折叠子-I53-50A的HMPV-F实施方式(SEQ ID NO：97)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVCTAAAVTCGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRALNKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTACGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYCLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTGGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
具有A113C、A120C、A339C、T160F、I177L和Q426C-F10的HMPV-F实施方式(SEQ IDNO：98)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCSDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVCTAAAVTCGVAIAKTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRALNKNKCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSGKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTACGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYCLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTGGSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
HMPV-F 115-BV(A185P)-折叠子-I53-50A实施方式(SEQ ID NO：99)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCADGPSLIKTELDLTKSALRELRTVSADQLAREEQIENPRRRRFVLGAIALGVATAAAVTAGVAIAKTIRLESEVTAIKNALKKTNEAVSTLGNGVRVLATAVRELKDFVSKNLTRAINKNKCDIPDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSEKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTAAGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPVKFPEDQFNVALDQVFESIENSQALVDQSNRILSSAEKGNTGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSHHHHHHHHGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
HMPV-F 115-BV(A185P)-I53-50A-F10实施方式(SEQ ID NO：100)
(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCADGPSLIKTELDLTKSALRELR(MSWKVVIIFSLLITPQHG)LKESYLEESCSTITEGYLSVLRTGWYTNVFTLEVGDVENLTCADGPSLIKTELDLTKSALRELRTVSADQLAREEQIENPRRRRFVLGAIALGVATAAAVTAGVAIAKTIRLESEVTAIKNALKKTNEAVSTLGNGVRVLATAVRELKDFVSKNLTRAINKNKCDIPDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSEKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTAAGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPVKFPEDQFNVALDQVFESIENSQALVDQSNRILSSAEKGNTGSGGSGSGEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGCTE
第二组件
本发明的纳米结构可以包含三聚体第一组件的多个拷贝和第二组件的多个拷贝。所述第二组件包含蛋白-蛋白界面，该界面诱导第二多肽的多个拷贝自缔合以形成第二组件。第二组件的多个低聚状态可以与纳米结构形式相容，该形式包括二聚体(两个拷贝)、三聚体(三个拷贝)、四聚体(四个拷贝)，五聚体(五个拷贝)、六聚体(六个拷贝)或更高的低聚状态。第二组件的每个拷贝还包含与三聚体组件结构域上的互补表面暴露界面相互作用的表面暴露界面。如King等人、Bale等人以及专利公开WO2014124301A1和US20160122392A1中所述，三聚体组件结构域和第二组件结构域之间的互补界面驱动将三聚体组件结构域和第二组件构域的多个拷贝组装成靶标纳米结构。在各种特定实施方式中：
(a)当每个第一多肽是DS-Cav1-折叠子-T33-31A(SEQ ID NO：69)或DS-Cav1-T33-31A(SEQ ID NO：70)时，每个第二多肽是T33-31B(SEQ ID NO：44)；
(b)当每个第一多肽是DS-Cav1-折叠子-T33-15B(SEQ ID NO：71)或DS-Cav1-T33-15B(SEQ ID NO：72)时，每个第二多肽是T33-15A(SEQ ID NO：45)；
(c)当每个第一多肽是DS-Cav1-折叠子-I53-50A(SEQ ID NO：73)或DS-Cav1-I53-50A(SEQ ID NO：74)时，每个第二多肽是I53-50B(SEQ ID NO：8)、I53-50B.1(SEQ ID NO：32)、I53-50B.1NegT2(SEQ ID NO：33)或I53-50B.4PosT1(SEQ ID NO：34)；
(d)当每个第一多肽是DS-Cav1-I32-28A(SEQ ID NO：75)时，每个第二多肽是I32-28B。
通过体外组装两个组分组装完全价态纳米结构
在一些实施方式中，纳米结构的每个三聚体第一组件均带有相同的作为基因融合体的F蛋白；这些纳米结构以完全价态显示F蛋白。这样的纳米结构是在称为体外组装工艺中从纯化的第一多肽和第二多肽产生的。在水性条件下，将纯化的包含F蛋白的三聚体第一多肽与适当的第二多肽以约1：1的摩尔比混合(见图1)。第二组件与三聚体第一组件相互作用以驱动靶标纳米结构的组件。通过用于评价蛋白或蛋白组件物理尺寸的常用生化或生物物理方法分析体外组装反应，可以确认靶标纳米结构的成功组装，该方法包括但不限于尺寸排阻色谱、天然(非变性)凝胶电泳、动态光散射、多角度光散射、分析超速离心、负染色电子显微镜、冷冻电子显微镜或X射线晶体学。如有必要，可以使用通常用于通过蛋白物理尺寸分离蛋白的制备技术，从体外组装反应中存在的其它种类或分子中纯化组装的纳米结构，该技术包括但不限于尺寸排阻色谱、制备性超速离心、切向流过滤或制备性凝胶电泳。可以通过通常用于确定水溶液中蛋白分子身份的技术来评价纳米结构中F蛋白的存在，该技术包括但不限于SDS-PAGE、质谱、蛋白测序或氨基酸分析。可以通过通常用于检测抗原存在和构象的技术评估F蛋白在粒子外部上的可及性及其构象或抗原性，该技术包括但不限于与单克隆抗体的结合、构象-特异性单克隆抗体或对抗原具有特异性的抗血清。
部分价态纳米结构的体外组装
在其它实施方式中，本发明的纳米结构包含带有作为基因融合体的F蛋白的三聚体第一组件以及一个或多个不带有作为基因融合体的F蛋白的三聚体第一组件的一个或多个拷贝；这些纳米结构以部分价态显示F蛋白。这些部分价态纳米结构是通过与第一多肽的混合物进行体外组装而产生的，其中带有作为基因融合体的F蛋白的三聚体第一组件的比例等于抗原在所得纳米结构中的期望价态。体外组装反应通常含有总第一多肽与总第二多肽的摩尔比为约1：1。作为非限制性示例，与三聚体组件的混合物进行体外组装反应，其中第一多肽的一半带有F蛋白，因为基因融合体会产生具有50％F蛋白价态的组装纳米结构。即，将占据纳米结构上F蛋白显示的可能位点的50％。作为非限制性示例，如果纳米结构是具有二十面体对称性的120个亚基组件，则该纳米结构包含20个总三聚体组成部分，并且50％价态的纳米结构显示可能20个F蛋白三聚体中的10个。以此方式，在体外组装反应中，带有F蛋白的第一多肽与缺少F蛋白的第一多肽的比例可以用于精确地调节所得纳米结构的F蛋白价态。本领域技术人员将理解的是，可以以这种手段调整平均价态；混合物中单个纳米结构的价态将围绕平均值分布。可以使用用于评估完全价态纳米结构的上文所述技术来评价这种部分价态纳米结构的成功组装，并且如有必要，可以使用用于纯化完全价态纳米结构的所述方法来纯化部分价态纳米结构。可以使用用于评估完全价态纳米结构中F蛋白存在的上文所述技术，通过定量分析来评价给定样品中带有F蛋白的第一多肽的平均价态。
共显示多种F蛋白的纳米结构的体外组装
在其它实施方式中，本发明的纳米结构包含两个或多个不同的第一多肽，所述第一多肽带有不同的F蛋白作为基因融合体。这些纳米结构在相同纳米结构上共显示多个不同的F蛋白。通过与第一多肽的混合物进行体外组装来产生这些多抗原纳米结构，其中每个第一多肽带有两个或多个不同的F蛋白中的一个作为基因融合体。混合物中每个第一多肽的比例决定了所得纳米结构中每个F蛋白的平均价态。体外组装反应通常含有总三聚体第一多肽与总第二多肽的摩尔比为约1：1。可以使用用于评估完全价态纳米结构中F蛋白存在的上文所述技术，通过定量分析来评价给定样品中每个带有F蛋白的第一多肽的存在和平均价态。
在各种实施方式中，纳米结构的直径在约20纳米(nm)至约40nm之间，内部腔跨度在约15nm至约32nm之间，并且蛋白壳在其最长维度上的孔径在约1nm至约14nm之间。
在一个实施方式中，该纳米结构具有二十面体对称性。在该实施方式中，该纳米结构可以包含第一多肽的60个拷贝和第二多肽的60个拷贝。在一个这样的实施方式中，每个第一组件中相同的第一多肽的数量不同于每个第二组件中相同的第二多肽的数量。例如，在一个实施方式中，纳米结构包含十二个第一组件和二十个第二组件；在该实施方式中，每个第一组件可以例如包含相同的第一多肽的五个拷贝，并且每个第二组件可以例如包含相同的第二多肽的三个拷贝。在另一个实施方式中，纳米结构包含十二个第一组件和三十个第二组件；在该实施方式中，每个第一组件可以例如包含相同的第一多肽的五个拷贝，并且每个第二组件可以例如包含相同的第二多肽的两个拷贝。在另一个实施方式中，纳米结构包含二十个第一组件和三十个第二组件；在该实施方式中，每个第一组件可以例如包含相同的第一多肽的三个拷贝，并且每个第二组件可以例如包含相同的第二多肽的两个拷贝。所有这些实施方式均能够形成具有规则二十面体对称性的合成纳米材料。在各种其它实施方式中，第一多肽和第二多肽的寡聚状态如下：
I53-34A：三聚体+I53-34B：五聚体；
I53-40A：五聚体+I53-40B：三聚体；
I53-47A：三聚体+I53-47B：五聚体；
I53-50A：三聚体+I53-50B：五聚体；
I53-51A：三聚体+I53-51B：五聚体；
I32-06A：二聚体+I32-06B：三聚体；
I32-19A：三聚体+I32-19B：二聚体；
I32-28A：三聚体+I32-28B：二聚体；
I52-03A：五聚体+I52-03B：二聚体；
I52-32A：二聚体+I52-32B：五聚体；和
I52-33A：五聚体+I52-33B：二聚体
在另一个实施方式中，本发明的任何实施方式或实施方式组合的纳米结构具有以下一个或多个特征，每个特征如在以下示例中所证明：
(a)结合融合前F特异性抗体(包括但不限于单克隆抗体25)；
(b)形成对称结构(包括但不限于二十面体结构)；
(c)在50℃下是稳定的；和/或
(d)在2.25M盐酸胍中是稳定的。
在另一方面，本发明提供了编码本发明融合蛋白的分离的核酸。分离的核酸序列可以包含RNA或DNA。如本文所用，“分离的核酸”是已经从基因组或cDNA序列的其正常周围核酸序列中除去的那些核酸。这种分离的核酸序列可以包含用于促进编码的蛋白表达和/或纯化的额外序列，包括但不限于polyA序列，修饰的Kozak序列以及编码表位标签、输出信号和分泌信号、核定位信号和质膜定位信号的序列。基于本文的教导，对于本领域技术人员而言显而易见的是，什么核酸序列将编码本发明的蛋白。
在另一方面，本发明提供了重组表达载体，其包含与合适的控制序列可操作地连接的本发明的任何实施方式或实施方式组合的分离的核酸。“重组表达载体”包括将核酸编码区或基因与能够影响基因产物表达的任何控制序列可操作地连接的载体。可操作地连接至本发明的核酸序列的“控制序列”是能够影响核酸分子表达的核酸序列。控制序列不必与核酸序列邻接，只要它们起指导其表达的作用即可。因此，例如，在启动子序列和核酸序列之间可以存在中间的未翻译但仍被转录的序列，并且仍然可以认为该启动子序列与编码序列“可操作地连接”。其它这种控制序列包括但不限于聚腺苷酸化信号、终止信号和核糖体结合位点。这些表达载体可以是本领域已知的任何类型，包括但不限于质粒和基于病毒的表达载体。用于驱动所公开的核酸序列在哺乳动物系统中表达的控制序列可以是组成型的(由多种启动子中的任意一个驱动，这些启动子包括但不限于CMV、SV40、RSV、肌动蛋白、EF)或诱导型的(由许多诱导型启动子中的任意一个驱动，这些启动子包括但不限于四环素响应性、蜕皮激素响应性、类固醇响应性的启动子)。用于转染原核细胞的表达载体的构建也是本领域众所周知的，因此可以通过标准技术来完成。(参见例如Sambrook,Fritsch和Maniatis,in:Molecular Cloning,A Laboratory Manual,Cold Spring HarborLaboratory Press,1989；Gene Transfer and Expression Protocols,pp.109-128,编辑E.J.Murray,The Humana Press Inc.,Clifton,N.J.),以及the Ambion 1998Catalog(Ambion,Austin,TX)。表达载体必须作为附加体或通过整合到宿主染色体DNA中才能在宿主生物体中复制。在一个优选的实施方式中，该表达载体包含质粒。然而，本发明旨在包括具有等价功能的其它表达载体，例如病毒载体。
在另一方面，本发明提供了已经用本文所公开的重组表达载体转染的宿主细胞，其中所述宿主细胞可以是原核或真核的，例如哺乳动物细胞。该细胞可以被瞬时或稳定地转染。可以通过本领域已知的任何技术将表达载体这样转染到原核和真核细胞中，该技术包括但不限于标准细菌转化、磷酸钙共沉淀、电穿孔或脂质体介导的转染、DEAE葡聚糖介导的转染、聚阳离子介导的转染、或病毒介导的转染。(参见例如Molecular Cloning:ALaboratory Manual(Sambrook,等人,1989,Cold Spring Harbor Laboratory Press；Culture of Animal Cells:A Manual of Basic Technique,第二次编辑(R.I.Freshney.1987.Liss,Inc.New York,NY))生产根据本发明的多肽的方法是本发明的另一部分。该方法包括以下步骤：(a)在有利于多肽表达的条件下培养根据本发明该方面的宿主，和(b)可选地回收表达的多肽。
在另一方面，本发明提供了一种免疫原性组合物，其包含有效量的本发明的任何实施方式或实施方式组合的纳米结构和药学上可接受的载体。该组合物可以包含(a)冻干保护剂；(b)表面活性剂；(c)膨胀剂；(d)张力调节剂；(e)稳定剂；(f)防腐剂和/或(g)缓冲剂。
在一些实施方式中，药物组合物中的缓冲剂是Tris缓冲剂、组氨酸缓冲剂、磷酸盐缓冲剂、柠檬酸盐缓冲剂或乙酸盐缓冲剂。该组合物还可以包含冻干保护剂，例如蔗糖、山梨糖醇或海藻糖。在某些实施方式中，该组合物包括防腐剂，例如苯扎氯铵、苄索铵、氯己定、苯酚、间甲酚、苯甲醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、氯丁醇、邻甲酚、对甲酚、氯甲酚、硝酸苯汞、硫柳汞、苯甲酸及其各种混合物。在其它实施方式中，该组合物包括膨胀剂，例如甘氨酸。在其它实施方式中，该组合物包括含表面活性剂，例如聚山梨酸酯-20、聚山梨酸酯-40、聚山梨酸酯-60、聚山梨酸酯-65、聚山梨酸酯-80、聚山梨酸酯-85、泊洛沙姆-188、脱水山梨醇单月桂酸酯、脱水山梨醇单棕榈酸酯、脱水山梨醇单硬脂酸酯、脱水山梨醇单油酸酯、脱水山梨醇三月桂酸酯，脱水山梨醇三硬脂酸酯，脱水山梨醇三油酸酯或其组合。该组合物还可以包括张力调节剂，例如使所述制剂与人血液基本上等渗或等渗的化合物。示例性张力调节剂包括蔗糖、山梨糖醇、甘氨酸，甲硫氨酸、甘露糖醇、葡萄糖、肌醇、氯化钠、精氨酸和精氨酸盐酸盐。在其它实施方式中，该组合物额外包括稳定剂，例如以冻干或液体形式基本上防止或减少纳米结构的化学和/或物理不稳定性的分子。示例性稳定剂包括蔗糖、山梨糖醇、甘氨酸、肌醇、氯化钠、甲硫氨酸、精氨酸和精氨酸盐酸盐。
纳米结构可以是组合物中的唯一活性剂，或组合物可以进一步包含一种或多种适于预期用途的其它试剂，包括但不限于通常刺激免疫系统并总体上改善免疫应答的佐剂。可以使用任何合适的佐剂。术语“佐剂”是指增强对抗原的免疫应答的化合物或混合物。示例性佐剂包括但不限于：Adju-PhosTM、AdjumerTM、白蛋白-肝素微粒、藻葡聚糖(AlgalGlucan)、藻蛋白(Algammulin)、明矾(Alum)、抗原制剂、AS-2佐剂、自体树突状细胞、自体PBMC、AvridineTM、B7-2、BAK、BAY R1005、布比卡因(Bupivacaine)、布比卡因盐酸盐、BWZL、骨化三醇、磷酸钙凝胶、CCR5肽、CFA、霍乱全毒素(CT)和霍乱毒素B亚基(CTB)、霍乱毒素A1-亚基-蛋白A D片段融合蛋白、CpG、CRL1005、含细胞因子的脂质体、D-Murapalmitine、DDA、DHEA、白喉类毒素、DL-PGL、DMPC、DMPG、DOC/明矾复合物、禽痘(Fowlpox)、弗氏完全佐剂、γ菊粉、格布佐剂(Gerbu Adjuvant)、GM-CSF、GMDP、hGM-CSF、hIL-12(N222L)、hTNF-α、IFA、pcDNA3中的IFN-γ、IL-12DNA、IL-12质粒、IL-12/GMCSF质粒(Sykes)、pcDNA3中的IL-2、IL-2/Ig质粒、IL-2/Ig蛋白、IL-4、pcDNA3中的IL-4、ImiquimodTM、ImmTherTM、含共刺激分子抗体的免疫脂质体、干扰素-γ、白细胞介素-1β、白细胞介素-12、白细胞介素-2、白细胞介素-7、ISCOM(s)TM、Iscoprep 7.0.3TM、钥孔血蓝蛋白(Keyhole Limpet Hemocyanin)、脂基佐剂、脂质体、氧氟沙星、LT(R192G)、LT-OA或LT口服佐剂、LT-R192G、LTK63、LTK72、MF59、MONTANIDE ISA 51、MONTANIDE ISA 720、MPL.TM.、MPL-SE、MTP-PE、MTP-PE脂质体、Murametide、Murapalmitine、NAGO、nCT天然霍乱毒素、非离子表面活性剂囊泡、霍乱毒素mCT-E112K的无毒突变体E112K、对羟基苯甲酸甲酯、pCIL-10、pCIL12、pCMVmCAT1、pCMVN、Peptomer-NP、Pleuran、PLG、PLGA、PGA和PLA、Pluronic L121、PMMA、PODDSTM、聚rA:聚rU、聚山梨酯80、耳蜗蛋白(Protein Cochleates)、QS-21、Quadri A皂苷、Quil-A、RehydragelHPA、Rehydragel LV、RIBI、Ribilike佐剂系统(MPL、TMD、CWS)、S-28463、SAF-1、Sclavo肽、Sendai蛋白脂质体、含Senda脂质体基质、Span 85、Specol、角鲨烷1、角鲨烷2、硬脂基酪氨酸、破伤风类毒素(TT)、TheramideTM、苏糖酰基鼠基二肽(TMDP)、Ty粒子和Walter Reed脂质体。佐剂的选择依赖于待治疗的受试者。优选地，使用药学上可接受的佐剂。
在另一方面，本发明提供了用于在受试者中对副粘病毒和/或肺炎病毒F蛋白产生免疫应答的方法，其包括向所述受试者施用有效量的本发明的任何实施方式或实施方式组合的免疫原性组合物以产生免疫应答。在另一方面，本发明提供了用于在受试者中治疗或预防副粘病毒和/或肺炎病毒感染的方法，其包括向所述受试者施用有效量的本发明的任何实施方式或实施方式组合的免疫原性组合物，从而治疗或预防受试者的副粘病毒和/或肺炎病毒感染。
在一个实施方式中，所述副粘病毒和/或肺炎病毒包含呼吸道合胞病毒。“呼吸道合胞病毒”和“RSV”是指导致呼吸系统疾病的负义单链RNA病毒，尤其是在儿童中。当该方法包含治疗RSV感染时，将免疫原性组合物施用于已经感染有RSV和/或患有表明该受试者可能已感染了RSV的症状(包括但不限于下呼吸道感染、上呼吸道感染、细支气管炎、肺炎、发烧、精神不振、食欲减退、反复喘息和哮喘)的受试者。如本文所用，“治疗”或“治愈”包括但不限于完成以下一项或多项：(a)降低受试者的副粘病毒和/或肺炎病毒滴度；(b)限制受试者的副粘病毒和/或肺炎病毒滴度的任何增加；(c)降低副粘病毒和/或肺炎病毒症状的严重程度；(d)限制或预防感染后副粘病毒和/或肺炎病毒症状的发展；(e)抑制副粘病毒和/或肺炎病毒症状的恶化；(f)限制或预防先前有副粘病毒和/或肺炎病毒感染症状的受试者中副粘病毒和/或肺炎病毒症状的复发；和/或促进母体的副粘病毒和/或肺炎病毒抗体传播给婴儿(母体免疫后)。
当该方法包含限制副粘病毒和/或肺炎病毒感染时，将免疫原性组合物预防性地施用于未知感染的但可能有暴露于副粘病毒和/或肺炎病毒的风险的受试者。如本文所用，“限制”意指限制有RSV感染风险的受试者的RSV感染。特别高危群体包括18岁以下的儿童(特别是3岁或3岁以下的婴儿)、65岁以上的成人以及患有任何类型的免疫缺陷的个体。
如本文所用，“有效量”是指有效治疗和/或限制RSV感染的免疫原性组合物的量。免疫原性组合物通常被配制成药物组合物，例如上文所公开的那些，并可以通过任何合适的途径(包括口服、胃肠外、通过吸入喷雾、直肠或局部)施用含有常规药学上可接受的载体、佐剂和赋形剂的剂量单位制剂。本文所用的术语“肠胃外”包括皮下、静脉内、动脉内、肌内、胸骨内、腱内、脊柱内、颅内、胸腔内、输注技术或腹膜内。也可以通过微球、脂质体、免疫刺激复合物(ISCOM)或其它微粒递送系统或被引入到合适组织(例如血液)中的缓释制剂来施用多肽组合物。可以调整剂量方案以提供最佳的期望应答(例如治疗性或预防性应答)。合适的剂量范围可以是例如0.1ug/kg-100mg F蛋白或其抗原片段/kg体重。可以单次推注来递送该组合物，或者可以如由主治医务人员确定的那样施用一次以上(例如2、3、4、5或更多次)。
在一个实施方式中，施用导致在受试者中产生副粘病毒和/或肺炎病毒中和抗体。在另一个实施方式中，中和抗体以至少9400的滴度(1/ID50)存在于受试者的血清中；在其它实施方式中，中和抗体以20000或30500的滴度存在于受试者的血清中。
实施例
方法：
包含F蛋白和三聚体组件结构域的三聚体组成部分的表达和筛选
从Genscript订购了包括和缺乏DS-Cav1融合体的三聚体组成部分的人密码子优化序列。将单组分纳米结构的组成部分(即I3-01)克隆到含有一个CMV启动子的pcDNA3.1载体(ThermoFisher Scientific)中，而将两组分纳米结构的组成部分(例如I53-50)克隆到含有CMV和EF-1α启动子的pBudCE4.1TM载体(ThermoFisher Scientific)中。通过使用聚乙烯亚胺(PEI)瞬时转染Expi293FTM细胞(ThermoFisher Scientific)来表达重组蛋白。转染后五天通过离心收获细胞培养物。使用细胞上清液的直接涂覆通过ELISA或通过夹心ELISA分析分泌的蛋白。简而言之，将96孔MaxiSorpTM平板(Nunc)用用于直接ELISA的细胞上清液或用于夹心ELISA的鼠抗His标签单克隆抗体(ThermoFisher Scientific)涂覆96孔MaxiSorpTM平板(Nunc)。使用人帕利珠单抗、MPE8、RSD5和D25单克隆抗体检测分泌的蛋白。用BD细胞固定液/细胞渗透液(BD Biosciences)将转染的Expi293F细胞固定并渗透化，与人帕利珠单抗、MPE8和D25单克隆抗体一起温育，并用Alexa Fluor 647共轭的抗人IgG抗体(Jackson ImmunoResearch)染色。用FACS FortessaTM流式细胞仪(BD Biosciences)对染色的细胞计数。使用FlowJoTM软件进行分析。常规测试细胞系的支原体污染。
DS-Cav1-I53-50A的表达和纯化
通过使用线性25kDa聚乙烯亚胺(PEI；Polysciences)瞬时转染293T(ATCC)细胞来生产慢病毒。简而言之，将4×106个细胞平铺到10cm组织培养平板上。24小时后，将3μgpsPAX2、1.5μg pMD2G(分别为AddgeneTM质粒#12260和#12259)和6μg慢病毒载体质粒在500μl稀释剂(5mM HEPES，150mM NaCl，pH＝7.05)和42μl PEI(1mg/ml)中混合并温育15分钟。然后将DNA/PEI复合物滴加到平板中。转染后48小时收获慢病毒，并通过8000g低速离心18小时将其浓缩100倍。在125mL摇瓶中进行靶标细胞系的转导，该摇瓶中的10mL生长培养基中含有10×106个细胞。向烧瓶中添加100uL 100x慢病毒，并将细胞在8％CO2中于37℃下摇动(225rpm)温育4-6小时。4-6小时后，将20mL生长培养基添加到摇瓶中。
每隔一天将转导的细胞扩增至1×106个细胞/ml的密度，直到最终培养尺寸达到4L。在测量最终细胞浓度(约5×106个细胞/mL)和存活率(约90％存活率)后，在总温育17天后收获培养基。通过低速离心收集培养上清液以从上清液中除去细胞。添加NaCl和NaN3至终浓度分别为250mM和0.02％。将上清液通过AKTA PureTM(GE Healthsciences)以5ml/min加载到5mL HisTrapTM FF Crude色谱柱(GE Healthsciences)上。将镍洗脱液施加于HiLoadTM 16/600Superdex 200pg色谱柱(GE Healthsciences)以通过尺寸排阻色谱法进一步纯化靶标蛋白。将尺寸排阻纯化的靶标蛋白在液氮中速冻并储存在-80℃下。
带有DS-Cav1的纳米结构的体外组装
通过将每种浓度为50μM的DS-Cav1-折叠子-I53-50A三聚体和I53-50B.4PT1五聚体混合并在4℃下振动温育过夜来制备100％价态粒子(每个二十面体纳米结构20个DS-Cav1三聚体)。在某些情况下，使用GE Sephacryl S-500HR 16/60色谱柱在包含25mM TrispH 8、250mM NaCl、5％甘油的缓冲液中，从体外组装反应中剩余的多余组分中纯化组装的纳米结构。在存在和不存在还原剂的情况下，通过SDS-PAGE分析样品负载和SEC级分。将峰级分合并，使用GE VivaspinTM 20 30kDa MWCO离心过滤器浓缩，并使用Agilent 8454分光光度计定量。
通过将分别为50、25和75μM的DS-Cav1-折叠子-I53-50A三聚体、I53-50A三聚体和I53-50B.4PosT1五聚体混合而制备66％价态粒子(每个二十面体纳米结构约14个DS-Cav1三聚体)。通过将分别为25、50和75μM的DS-Cav1-折叠子-I53-50A三聚体、I53-50A三聚体和I53-50B.4PosT1五聚体混合而制备33％价态粒子(每个二十面体纳米结构约7个DS-Cav1三聚体)。允许体外组装反应在4℃下振动温育过夜。在某些情况下，使用GE SephacrylTM S-500HR 16/60色谱柱在包含25mM Tris pH 8、250mM NaCl、5％甘油的缓冲液中，从体外组装反应中剩余的多余组分中纯化组装的纳米结构。在存在和不存在还原剂的情况下，通过SDS-PAGE分析样品负载和SEC级分。将峰级分合并，使GE VivaspinTM 20 30kDa MWCO离心过滤器浓缩，并在4℃下以约21000g离心10分钟后，使用Agilent 8454分光光度计定量。然后将样品以1mL等分试样转移到33％价态粒子为1.1mg/mL和66％价态粒子为0.6mg/mL的低温试管中，在液氮中速冻并保存在-80℃下。
带有DS-Cav1的纳米结构的电子显微镜
通过使用25mM Tris pH 8、250mM NaCl、5％甘油稀释至0.01mg/mL制备用于阴性染色EM的样品，将3.5μL在辉光放电的铜碳涂覆的栅格上温育20秒，然后用一张Whatman1号滤纸将液体吸干。在将样品吸干后的几秒钟内，沉积3.5μL的染色剂液滴(2％w/v甲酸铀酰)并立即将其吸干，然后进行第二次染色/吸干周期。
圆二色谱(CD)分光旋光法
将来自F蛋白(0.5mg ml-1)的CD光谱记录在ChirascanTM分光旋光计(AppliedPhotophysics)上，其上波长范围为195nm至260nm、带宽为1nm、步长为0.5nm、每步1s。远紫外线区域的光谱平均需要进行3次扫描，并从用缓冲液进行的空白光谱中减去。在每个温度下平衡1分钟后，通过以1℃的间隔进行扫描来监测热变性。将数据拟合成简单的一阶曲线。ΔA222的值在y轴上表示为在20℃下记录值的百分比。
酶联免疫吸附测定(ELISA)
为了测试抗体或血清的特异性结合，用连续稀释的来自细胞的组织培养上清液涂覆96孔MaxiSorpTM平板(Nunc)，该细胞表达包含F蛋白和三聚体组件结构域或2μg ml-1以下纯化的蛋白的三聚体组成部分：具有折叠子的Ds-Cav1、融合至三聚体第一多肽的Ds-Cav1或显示纳米结构的DS-Cav1。用1％牛血清白蛋白(BSA)封闭平板，并与滴定的抗体(D25、MPE8、帕利珠单抗、RSD5)或鼠血清一起温育，然后与AP共轭的山羊抗人IgG(SouthernBiotech，2040-04)或山羊抗小鼠IgG(Southern Biotech，1030-04)一起温育。然后用PBS缓冲液(Gibco，Invitrogen)、0.05％吐温20洗涤平板，并添加底物(p-NPP，Sigma)，在405nm下读取平板。
表面等离子体共振(SPR)
在ProteONTM XPR-36仪器(Bio-Rad Laboratories)上于25℃下在PBS缓冲液(Gibco，Invitrogen)、0.05％吐温20中进行实验。通过胺偶联以1000个应答单位(RU)将D25单克隆抗体(mAb)固定在GLM传感器芯片表面上，并在相同的偶联条件下创建没有蛋白的空白表面用作参考。将单克隆抗体(D25、MPE8、帕利珠单抗和131-2a)以100μl/min流速以50nM浓度注射到不同传感器通道中。使用Proteon软件处理数据，通过减去空白表面并在局部拟合数据之前仅缓冲注射进行双重参考。
疫苗接种和血清学分析
6-9周龄的雌性BALB/c小鼠获自ENVIGO Laboratories(意大利)。所有蛋白均按照制造商的说明书使用AddaVaxTM佐剂(Invivogen)来配制。在第0、14和28天，用相当于PBS中50％AddaVaxTM中5μg DS-Cav1抗原当量的总蛋白剂量对小鼠进行皮下(s.c)免疫。在第24天和第40天将小鼠放血。将回收的血清用于测量结合和中和滴度。通过涂覆3μg/ml DS-Cav1、I53-50纳米结构或I53-50纳米结构亚基来测量结合滴度。
病毒中和测定和显微镜分析
使用基于微中和流式细胞仪的测定测量血清对RSV感染的中和。在37℃下将系列稀释的血清与RSV预温育1小时，然后添加到96孔平底平板中的10000个Hep-2(CCL-23TM)细胞/孔中(MOI为1)。24小时后，将细胞洗涤、分离并用2％甲醛固定。通过具有偶联至自动化平台的Intellicyt的高通量FACS测量GFP阳性细胞的百分比。通过Prism 7(GraphPad Software)的非线性回归计算中和50％感染(TCID50)的组织培养抑制稀释(TCID)。
非人灵长类动物(NHP)免疫
用配制在MF59样佐剂SWE中的三聚体DS-Cav1(50μg；n＝4)或DS-Cav1-折叠子-I53-50纳米结构(96μg，其包含50μg显示的DS-Cav1；n＝5)在第0和第4周立即将恒河猕猴免疫(右股四头肌)。在第6和16周获得血清用于血清学分析。
通过相对结合D25而带有DS-Cav1的纳米结构的稳定性
在ProteONTM XPR-36仪器(Bio-Rad Laboratories)上于20℃下在PBS缓冲液(Gibco，Thermo Fisher Scientific)和0.05％吐温20(Sigma)中进行实验。通过胺偶联(EDC/NHS化学)将100nM D25抗体固定在GLM传感器芯片表面上，并在相同的偶联条件下创建没有抗体的空白表面用作参考。将在不同温度(20、50、70或80℃)下受热1小时的分析蛋白(可溶性DS-Cav1、可溶性DS-Cav1-I53-50A和DS-Cav1-折叠子-I53-50纳米结构)以100μl/min流速以50nM浓度注射到不同传感器通道中。使用Proteon软件处理数据，通过减去空白表面并在局部拟合数据之前仅缓冲注射进行双重参考。
纳米结构相关蛋白的化学变性
随着盐酸胍浓度范围从0M至6.5M不同且以0.25M的增量递增，在25mM Tris pH 8、250mM NaCl、5％甘油中将三聚体DS-Cav1、DS-Cav1-I53-50A、DS-Cav1-I53-50、I53-50、三聚体I53-50A或五聚体I53-50B.4PT1稀释至最终浓度为2.5μM。一式三份制备样品并在环境温度下温育16小时。在Cary Eclipse荧光分光光度计上，测量每种蛋白和每个重复的每种盐酸胍浓度的固有荧光。在所有实验中，将Peltier控制器用于池架以保持25℃的温度。使用10mm池(Agilent Cuvette，部件号6610021600)收集荧光光谱，在290nm处激发并以1nm的带通以60nm/分钟的速率从310nm扫描发射到510nm。
统计分析
没有使用统计方法来确定样本量。当将三个或更多个组比较时，数据通过Prism 6(GraphPadTM软件)使用两尾无参数Mann-Whitney U检验进行两组比较，或使用Kruskall-Wallis检验(和Dunn的后检验)进行分析。
结果
包含F蛋白和三聚体组件结构域的三聚体组成部分
由ELISA测定中的融合前特异性单克隆抗体结合判断，发现了几个三聚体组成部分(每个都包含基因融合至三聚体组件结构域的F蛋白)均分泌自具有其F蛋白处于折叠良好的融合前构象的HEK293F细胞。图2显示了ELISA数据的示例，该数据分析了表达DS-Cav1-折叠子、DS-Cav1-折叠子-T33-31A和DS-Cav1-T33-31A的HEK293F细胞的上清液。几个其它三聚体组成部分可产生折叠良好的融合前F蛋白的可检测分泌物。
DS-Cav1-折叠子-I53-50A的表达和纯化
将编码DS-Cav1-折叠子-I53-50A的慢病毒载体用于转导HEK293F细胞以进行大规模表达。通过固定的金属亲和色谱和尺寸排阻色谱从组织培养上清液中纯化分泌的蛋白。尺寸排阻色谱(图3)表明了纯化的蛋白形成单个单分散种类。
I53-50B.4PT1的表达和纯化
如Bale等人和专利公开US20160122392A1中所述的表达和纯化五聚体蛋白I53-50B.4PT1，其包含与I53-50A或DS-Cav1-折叠子-I53-50A中的三聚体组件结构域相互作用以驱动基于二十面体I53-50的纳米结构组装的第二组件结构域。
带有DS-Cav1的I53-50纳米结构的体外组装和表征
如Bale等人最近所述，I53-50是具有二十面体对称性的120个亚基的两组分纳米结构，其包含20个三聚体(I53-50A)和12个五聚体(I53-50B)组成部分。I53-50A的N末端暴露在I53-50纳米结构的外部上，这使抗原能够通过与I53-530A N末端的基因传融合而在纳米结构外部上显示。通过以不同的摩尔比混合两种纯化的蛋白将纯化的DS-Cav1-折叠子-I53-50A和I53-50B.4PT1体外组装以形成在纳米结构外部上显示各种量DS-Cav1的120个亚基的二十面体纳米结构。在单独的制备中，如上所述制得了以100％(20个三聚体)、66％(约14个三聚体)和33％(约7个三聚体)的价态显示DS-Cav1的纳米结构。通过几种技术评价过夜温育后体外组装反应中存在的种类，该技术包括尺寸排阻色谱-多角度光散射(SEC-MALS)、动态光散射和紫外线(UV)/可见(vis)光谱。使用尺寸排阻色谱从体外组装反应中纯化了120个亚基的纳米结构(图4中呈现了使用100％价态纳米结构获得的示例性色谱)。通过负染色电子显微镜表征纯化的纳米结构，这揭示了其中由于尖峰从核心二十面体I53-50组件向外突出而使DS-Cav1清晰可见的单分散粒子场(使用100％价态粒子获得的示例性显微照片呈现于如图5中)。使用对融合前构象具有特异性的单克隆抗体的ELISA测定证实了如此显示在纳米结构外部上的DS-Cav1折叠良好且具有抗原性完整(图6)。评估单克隆抗体结合动力学的表面等离振子共振实验揭示了抗体从100％价态的DS-Cav1-折叠子-I53-50纳米结构上解离比从DS-Cav1-折叠子三聚体中解离的慢，这可能是由于亲和力效应源自DS-Cav1在纳米结构外部上的多价态呈现(图6)。总之，这些实验证实了DS-Cav1-折叠子-I53-50纳米结构形成了单分散的二十面体纳米结构，在其外部上显示折叠良好的，抗原性完整的DS-Cav1三聚体。这些发现激发了实验以评估DS-Cav1-折叠子-I53-50纳米结构作为用于诱导动物针对DS-Cav1的体液免疫应答的免疫原的实用性。
DS-Cav1-折叠子-I53-50纳米结构的免疫原性
使用如上文所述的初免(prime-boost)策略将显示33％、66％和100％价态DS-Cav1的DS-Cav1-折叠子-I53-50纳米结构注射到小鼠中。另外的小鼠组用三聚体DS-Cav1-折叠子作为纳米结构或I53-50纳米结构对DS-CAV1诱导的体液免疫应答的基准，所述I53-50纳米结构缺乏显示DS-CAV1作为DS-CAV1特异性应答的阴性对照。将注射后在所定义的时间点从小鼠提取的血清的ELISA测定用于测量注射动物血清中存在的DS-Cav1特异性抗体滴度(图7)。如预期的那样，注射有缺乏显示DS-Cav1的I53-50纳米结构的动物血清中不含有对DS-Cav1特异性的抗体。根据先前的结果(McClellan等人)，三聚体DS-Cav1折叠子诱导了DS-Cav1特异性抗体。价态33％、66％和100％的DS-Cav1纳米结构均比三聚体DS-Cav1折叠子诱导更高的DS-Cav1特异性抗体滴度，且抗体滴度随DS-Cav1价态的增加而增加。与DS-Cav1相比，注射有100％价态DS-Cav1-折叠子-I53-50纳米结构的小鼠中，DS-Cav1特异性滴度平均高出约2.5倍。这些结果证明了当将其注入到动物中时，副粘病毒F蛋白在自组装蛋白纳米结构上多价态显示的免疫原可以诱导更高的体液免疫应答。
还使用标准中和测定在HEp-2细胞中评估了注射有上文所述一系列免疫原的小鼠血清的中和抗体滴度的存在(图8)。血清中和抗体滴度的趋势与DS-Cav1特异性结合抗体滴度中所观察到的趋势高度相关。注射有缺乏显示DS-Cav1的I53-50纳米结构动物血清不能中和病毒，这与这些血清中缺乏DS-Cav1特异性抗体一致。注射有三聚体DS-Cav-1-折叠子中和病毒的动物血清的平均滴度(1/ID50)为3030。33％、66％和100％价态的DS-Cav1-I53-50纳米结构比三聚体DS-Cav1-折叠子诱导了更高的中和抗体滴度，平均滴度分别为9400、20000和30500。这些结果证明了由免疫原诱导的更高的体液应答导致更有效的病毒中和，在该免疫原中副粘病毒F蛋白多价态地显示在自组装蛋白纳米结构上。
还将DS-Cav1-折叠子-I53-50纳米结构注射到恒河猴中以评估它们在灵长类动物免疫系统中的免疫原性。在第0和第4周向动物肌肉内注射以100％价态DS-Cav1显示的游离DS-Cav1三聚体或DS-Cav1-折叠子-I53-50纳米结构。在这两种情况下，DS-Cav1抗原的剂量均为50μg，并用MF59类角鲨烯基水包油乳液佐剂SWE配制免疫原。评估在第6和16周时从动物获得的血清的抗DS-Cav1抗体滴度和RSV中和抗体滴度(图9)。该结果反映了在小鼠中获得的结果。在第16周，与注射有三聚体DS-Cav1的动物相比，注射有DS-Cav1-折叠子-I53-50纳米结构的动物的平均抗DS-Cav1抗体滴度高4倍。在第16周，与注射有三聚体DS-Cav1的动物相比，注射有DS-Cav1-折叠子-I53-50纳米结构的动物的RSV中和抗体滴度高16倍。这些结果证明了在灵长类动物免疫系统中，其中与单独的三聚体副粘病毒F蛋白相比，在自组装蛋白纳米结构上多价态地显示副粘病毒F蛋白的免疫原诱导更强烈的体液免疫应答(包括高水平的病毒中和抗体)。
通过融合至I53-50A的DS-Cav1的物理稳定性
鉴于融合前F的关键抗原特性，我们使用两种正交方法来测量当融合至I53-50A时和/或当进一步组装成二十面体纳米结构时的DS-Cav1的物理稳定性。首次测定是在热应激后测量了融合前特异性单克隆抗体结合的保持力，该方法先前已用于表征融合前F的稳定性(McLellan等人2013；Joyce等人2016；Krarup等人2015)。将含有等价浓度(50nM)DS-Cav1的三聚DS-Cav1、三聚DS-Cav1-I53-50A和DS-Cav1-I53-50纳米结构的样品分为四个等分试样，并在20、50、70或80℃下温育1小时。冷却至室温后，通过表面等离子体共振(SPR)测定D25结合。我们发现所有样品在20和50℃下均等价地结合D25，但在80℃下1小时后失去与D25的大部分反应性，如先前针对DS-Cav1的报道(McLellan等人2013；Joyce等人2016)(图10)。有趣的是，尽管D25也不能结合在70℃下温育1小时的三聚体DS-Cav1，但三聚体DS-Cav1-I53-50A和DS-Cav1-I53-50纳米结构保留了各自结合信号的50％和80％(图10)。尽管DS-Cav1-I53-50纳米结构的多价态性质使与三聚体DS-Cav1的直接定量比较变得复杂，但这些结果表明了与I53-50A三聚体的基因融合进一步稳定了DS-Cav1的融合前构象，这暗示了在组装的纳米结构免疫原的情况下保持增加的稳定性。
我们使用盐酸胍(GdnHCl)中的化学变性(通过固有的色氨酸荧光监测)作为第二种独立于抗体的技术来评估物理稳定性。分析在0-6.5M GdnHCl中温育的DS-Cav1的荧光发射揭示了该蛋白质经历了两个微妙的不同跃迁，一个在0.25M和2.25M GdnHCl之间，另一个在2.25M和5.75M之间(图11)。相反，三聚体DS-Cav1-I53-50A仅出现一个单一跃迁，发生在2.25M和6.25M GdnHCl之间(图11)。目前尚不清楚三聚体DS-Cav1-I53-50A是否缺少DS-Cav1在所观察到的较低[GdnHCl]处的跃迁，还是只是转变为较高的[GdnHCl]。然而，很明显地，通过与三聚体I53-50A的基因融合来稳定DS-Cav1的天然构象，这反映了通过测量热应激后D25结合而获得的结果。比较DS-Cav1-I53-50纳米结构和单独的I53-50纳米结构(缺少融合的DS-Cav1)的数据表明了在组装成二十面体纳米结构时可以保持稳定性(图11)。这种影响的根源可能是I53-50A三聚体的极端稳定性。I53-50A源自嗜热细菌T.maritima的KDPG醛缩酶。并且仅在非常高的GdnHCl浓度(≥5.75M)下才开始显示荧光变化(图11)。
我们进行了额外的构建以评价GS重复的数量以及对稳定性结构域(例如折叠子部分)的需要。
序列信息
IPD名称 MS(Da) 构建体信息
RSV_F-10 74005.38 DS-Cav1-8GS-HelExt-50A
RSV_F-11 74293.64 DS-Cav1-12GS-HelExt-50A
RSV_F-12 74551.87 DS-Cav1-16GS-HelExt-50A
RSV_F-13 77212.97 DS-Cav1-折叠子-10GS-HelExt-50A
RSV_F-14 77558.28 DS-Cav1-折叠子-15GS-HelExt-50A
RSV_F-15 77933.62 DS-Cav1-折叠子-20GS-HelExt-50A
研究基于小规模瞬时转染中的表达产量。将能够表达相关构建体的质粒转化到NEB5α大肠杆菌细胞中，并在LB+羧苄青霉素琼脂平板上选择。通过用细菌菌落接种TB培养基并再用50ug/mL羧苄青霉素选择来制备1mL培养物。按照其方案将Qiagen Mini Prep试剂盒用于纯化来自大肠杆菌培养物的质粒。将Expi293FTM细胞(ThermoFisher)在添加了青霉素(100u/mL)和链霉素(100μg/mL)的Expi293TM表达培养基(ThermoFisher)中以8％CO2、37℃和125rpm摇动进行培养。
转染前一天，以2E6个细胞/mL的浓度接种细胞。转染当天，通过带有台盼蓝的Countess II(ThermoFisher)对细胞计数以确定细胞存活率。将细胞浓度调节至2.5E6个细胞/mL，并将细胞以1mL体积平铺到未处理的12孔板(Corning)中。按照制造商的说明，使用ExpifectamineTM(ThermoFisher)将每个孔转染1μg DNA质粒。转染后18小时，添加ThermoFisher的ExpifectamineTM转染试剂盒组分的增强剂。转染后5天收获1mL培养物，并通过在4℃下以1500xg离心5分钟从上清液中沉淀出细胞。上清液通过带有PVDF膜的0.45μM过滤器过滤。
将含有DS-Cav1-I53-50A构建体的过滤上清液变性，并在含2巯基乙醇的2xLaemmli缓冲液中于95℃下煮沸10分钟。SDS-PAGE分离了样品级分，然后将其转移到硝酸纤维素膜上，并先用帕利珠单抗探测，再用二抗(与HRP共轭的抗人抗体)探测。使用ClarityWestern ECL印迹底物(Bio-Rad)对印迹成像。
将含有DS-Cav1-I53-50A构建体的滤过上清液以两倍稀释系列与Nunc MaxiSorpTM96孔板结合。融合前构象特异性抗体D25用于检测DS-Cav1-I53-50A，然后检测与HRP共轭的第二抗人抗体。通过底物TMB比色法确定蛋白产量，并在450nm处收集吸光度。
融合前特异性单克隆抗体(mAb)D25的表达产量和结合(数据未显示)表明所有构建体表达良好并且处于融合前构象。本领域技术人员将预期，异源三聚化结构域(例如折叠子)将需要用于融合前F构建体的正确表达和折叠。我们的结果表明I53-50A纳米结构组分可以支持DS-Cav1的表达和正确折叠，而无需使用三聚化结构域(例如折叠子)。D25与这些构建体的结合表明它们具有完整的抗原性，并预期诱导有效的免疫应答(包括中和抗体)，类似于包含DS-Cav1-折叠子-I53-50融合多肽的纳米结构。
序列表
<110> 华盛顿大学
生物医学研究所
N·P·金
D·贝克
B·尼克森
L·J·斯图尔特
L·佩雷斯
A·兰扎韦基亚
J·马坎达力
<120> 显示副粘病毒和/或肺炎病毒F蛋白的自组装蛋白纳米结构及其用途
<130> 17-341-PCT
<150> US 62/481,331
<151> 2017-04-01
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<213> 人工序列
<220>
<223> I53-50A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 7
Met Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu
1 5 10 15
Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe
20 25 30
Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala
35 40 45
Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile
50 55 60
Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val
65 70 75 80
Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile
85 90 95
Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met
100 105 110
Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu
115 120 125
Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met
130 135 140
Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn
145 150 155 160
Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly
165 170 175
Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys
180 185 190
Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
195 200 205
<210> 8
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-50B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 8
Met Asn Gln His Ser His Lys Asp Tyr Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala
20 25 30
Phe Glu Ala Ala Met Ala Asp Ile Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Asp Gly Met Met Asn Val Gln Leu Ser Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Arg Tyr Arg Asp Ser Asp Ala His Thr Leu
115 120 125
Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala
130 135 140
Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 9
<211> 177
<212> PRT
<213> 人工序列
<220>
<223> I53-51A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 9
Met Phe Thr Lys Ser Gly Asp Asp Gly Asn Thr Asn Val Ile Asn Lys
1 5 10 15
Arg Val Gly Lys Asp Ser Pro Leu Val Asn Phe Leu Gly Asp Leu Asp
20 25 30
Glu Leu Asn Ser Phe Ile Gly Phe Ala Ile Ser Lys Ile Pro Trp Glu
35 40 45
Asp Met Lys Lys Asp Leu Glu Arg Val Gln Val Glu Leu Phe Glu Ile
50 55 60
Gly Glu Asp Leu Ser Thr Gln Ser Ser Lys Lys Lys Ile Asp Glu Ser
65 70 75 80
Tyr Val Leu Trp Leu Leu Ala Ala Thr Ala Ile Tyr Arg Ile Glu Ser
85 90 95
Gly Pro Val Lys Leu Phe Val Ile Pro Gly Gly Ser Glu Glu Ala Ser
100 105 110
Val Leu His Val Thr Arg Ser Val Ala Arg Arg Val Glu Arg Asn Ala
115 120 125
Val Lys Tyr Thr Lys Glu Leu Pro Glu Ile Asn Arg Met Ile Ile Val
130 135 140
Tyr Leu Asn Arg Leu Ser Ser Leu Leu Phe Ala Met Ala Leu Val Ala
145 150 155 160
Asn Lys Arg Arg Asn Gln Ser Glu Lys Ile Tyr Glu Ile Gly Lys Ser
165 170 175
Trp
<210> 10
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-51B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 10
Met Asn Gln His Ser His Lys Asp Tyr Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Asp Ile Val Asp Gln Cys Val Arg Ala
20 25 30
Phe Glu Glu Ala Met Ala Asp Ala Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Asp Gly Met Met Asn Val Gln Leu Ser Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Arg Tyr Arg Ser Ser Arg Glu His His Glu
115 120 125
Phe Phe Arg Glu His Phe Met Val Lys Gly Val Glu Ala Ala Ala Ala
130 135 140
Cys Ile Thr Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 11
<211> 201
<212> PRT
<213> 人工序列
<220>
<223> I52-03A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 11
Met Gly His Thr Lys Gly Pro Thr Pro Gln Gln His Asp Gly Ser Ala
1 5 10 15
Leu Arg Ile Gly Ile Val His Ala Arg Trp Asn Lys Thr Ile Ile Met
20 25 30
Pro Leu Leu Ile Gly Thr Ile Ala Lys Leu Leu Glu Cys Gly Val Lys
35 40 45
Ala Ser Asn Ile Val Val Gln Ser Val Pro Gly Ser Trp Glu Leu Pro
50 55 60
Ile Ala Val Gln Arg Leu Tyr Ser Ala Ser Gln Leu Gln Thr Pro Ser
65 70 75 80
Ser Gly Pro Ser Leu Ser Ala Gly Asp Leu Leu Gly Ser Ser Thr Thr
85 90 95
Asp Leu Thr Ala Leu Pro Thr Thr Thr Ala Ser Ser Thr Gly Pro Phe
100 105 110
Asp Ala Leu Ile Ala Ile Gly Val Leu Ile Lys Gly Glu Thr Met His
115 120 125
Phe Glu Tyr Ile Ala Asp Ser Val Ser His Gly Leu Met Arg Val Gln
130 135 140
Leu Asp Thr Gly Val Pro Val Ile Phe Gly Val Leu Thr Val Leu Thr
145 150 155 160
Asp Asp Gln Ala Lys Ala Arg Ala Gly Val Ile Glu Gly Ser His Asn
165 170 175
His Gly Glu Asp Trp Gly Leu Ala Ala Val Glu Met Gly Val Arg Arg
180 185 190
Arg Asp Trp Ala Ala Gly Lys Thr Glu
195 200
<210> 12
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> I52-03B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 12
Met Tyr Glu Val Asp His Ala Asp Val Tyr Asp Leu Phe Tyr Leu Gly
1 5 10 15
Arg Gly Lys Asp Tyr Ala Ala Glu Ala Ser Asp Ile Ala Asp Leu Val
20 25 30
Arg Ser Arg Thr Pro Glu Ala Ser Ser Leu Leu Asp Val Ala Cys Gly
35 40 45
Thr Gly Thr His Leu Glu His Phe Thr Lys Glu Phe Gly Asp Thr Ala
50 55 60
Gly Leu Glu Leu Ser Glu Asp Met Leu Thr His Ala Arg Lys Arg Leu
65 70 75 80
Pro Asp Ala Thr Leu His Gln Gly Asp Met Arg Asp Phe Gln Leu Gly
85 90 95
Arg Lys Phe Ser Ala Val Val Ser Met Phe Ser Ser Val Gly Tyr Leu
100 105 110
Lys Thr Val Ala Glu Leu Gly Ala Ala Val Ala Ser Phe Ala Glu His
115 120 125
Leu Glu Pro Gly Gly Val Val Val Val Glu Pro Trp Trp Phe Pro Glu
130 135 140
Thr Phe Ala Asp Gly Trp Val Ser Ala Asp Val Val Arg Arg Asp Gly
145 150 155 160
Arg Thr Val Ala Arg Val Ser His Ser Val Arg Glu Gly Asn Ala Thr
165 170 175
Arg Met Glu Val His Phe Thr Val Ala Asp Pro Gly Lys Gly Val Arg
180 185 190
His Phe Ser Asp Val His Leu Ile Thr Leu Phe His Gln Arg Glu Tyr
195 200 205
Glu Ala Ala Phe Met Ala Ala Gly Leu Arg Val Glu Tyr Leu Glu Gly
210 215 220
Gly Pro Ser Gly Arg Gly Leu Phe Val Gly Val Pro Ala
225 230 235
<210> 13
<211> 138
<212> PRT
<213> 人工序列
<220>
<223> I52-32A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 13
Met Gly Met Lys Glu Lys Phe Val Leu Ile Ile Thr His Gly Asp Phe
1 5 10 15
Gly Lys Gly Leu Leu Ser Gly Ala Glu Val Ile Ile Gly Lys Gln Glu
20 25 30
Asn Val His Thr Val Gly Leu Asn Leu Gly Asp Asn Ile Glu Lys Val
35 40 45
Ala Lys Glu Val Met Arg Ile Ile Ile Ala Lys Leu Ala Glu Asp Lys
50 55 60
Glu Ile Ile Ile Val Val Asp Leu Phe Gly Gly Ser Pro Phe Asn Ile
65 70 75 80
Ala Leu Glu Met Met Lys Thr Phe Asp Val Lys Val Ile Thr Gly Ile
85 90 95
Asn Met Pro Met Leu Val Glu Leu Leu Thr Ser Ile Asn Val Tyr Asp
100 105 110
Thr Thr Glu Leu Leu Glu Asn Ile Ser Lys Ile Gly Lys Asp Gly Ile
115 120 125
Lys Val Ile Glu Lys Ser Ser Leu Lys Met
130 135
<210> 14
<211> 154
<212> PRT
<213> 人工序列
<220>
<223> I52-32B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 14
Met Lys Tyr Asp Gly Ser Lys Leu Arg Ile Gly Ile Leu His Ala Arg
1 5 10 15
Trp Asn Leu Glu Ile Ile Ala Ala Leu Val Ala Gly Ala Ile Lys Arg
20 25 30
Leu Gln Glu Phe Gly Val Lys Ala Glu Asn Ile Ile Ile Glu Thr Val
35 40 45
Pro Gly Ser Phe Glu Leu Pro Tyr Gly Ser Lys Leu Phe Val Glu Lys
50 55 60
Gln Lys Arg Leu Gly Lys Pro Leu Asp Ala Ile Ile Pro Ile Gly Val
65 70 75 80
Leu Ile Lys Gly Ser Thr Met His Phe Glu Tyr Ile Cys Asp Ser Thr
85 90 95
Thr His Gln Leu Met Lys Leu Asn Phe Glu Leu Gly Ile Pro Val Ile
100 105 110
Phe Gly Val Leu Thr Cys Leu Thr Asp Glu Gln Ala Glu Ala Arg Ala
115 120 125
Gly Leu Ile Glu Gly Lys Met His Asn His Gly Glu Asp Trp Gly Ala
130 135 140
Ala Ala Val Glu Met Ala Thr Lys Phe Asn
145 150
<210> 15
<211> 164
<212> PRT
<213> 人工序列
<220>
<223> I52-33A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 15
Met Ala Val Lys Gly Leu Gly Glu Val Asp Gln Lys Tyr Asp Gly Ser
1 5 10 15
Lys Leu Arg Ile Gly Ile Leu His Ala Arg Trp Asn Arg Lys Ile Ile
20 25 30
Leu Ala Leu Val Ala Gly Ala Val Leu Arg Leu Leu Glu Phe Gly Val
35 40 45
Lys Ala Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu
50 55 60
Pro Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys
65 70 75 80
Pro Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Lys Gly Ser Thr
85 90 95
Met His Phe Glu Tyr Ile Cys Asp Ser Thr Thr His Gln Leu Met Lys
100 105 110
Leu Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Leu Thr Cys
115 120 125
Leu Thr Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys
130 135 140
Met His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala
145 150 155 160
Thr Lys Phe Asn
<210> 16
<211> 175
<212> PRT
<213> 人工序列
<220>
<223> I52-33B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 16
Met Gly Ala Asn Trp Tyr Leu Asp Asn Glu Ser Ser Arg Leu Ser Phe
1 5 10 15
Thr Ser Thr Lys Asn Ala Asp Ile Ala Glu Val His Arg Phe Leu Val
20 25 30
Leu His Gly Lys Val Asp Pro Lys Gly Leu Ala Glu Val Glu Val Glu
35 40 45
Thr Glu Ser Ile Ser Thr Gly Ile Pro Leu Arg Asp Met Leu Leu Arg
50 55 60
Val Leu Val Phe Gln Val Ser Lys Phe Pro Val Ala Gln Ile Asn Ala
65 70 75 80
Gln Leu Asp Met Arg Pro Ile Asn Asn Leu Ala Pro Gly Ala Gln Leu
85 90 95
Glu Leu Arg Leu Pro Leu Thr Val Ser Leu Arg Gly Lys Ser His Ser
100 105 110
Tyr Asn Ala Glu Leu Leu Ala Thr Arg Leu Asp Glu Arg Arg Phe Gln
115 120 125
Val Val Thr Leu Glu Pro Leu Val Ile His Ala Gln Asp Phe Asp Met
130 135 140
Val Arg Ala Phe Asn Ala Leu Arg Leu Val Ala Gly Leu Ser Ala Val
145 150 155 160
Ser Leu Ser Val Pro Val Gly Ala Val Leu Ile Phe Thr Ala Arg
165 170 175
<210> 17
<211> 208
<212> PRT
<213> 人工序列
<220>
<223> I32-06A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 17
Met Thr Asp Tyr Ile Arg Asp Gly Ser Ala Ile Lys Ala Leu Ser Phe
1 5 10 15
Ala Ile Ile Leu Ala Glu Ala Asp Leu Arg His Ile Pro Gln Asp Leu
20 25 30
Gln Arg Leu Ala Val Arg Val Ile His Ala Cys Gly Met Val Asp Val
35 40 45
Ala Asn Asp Leu Ala Phe Ser Glu Gly Ala Gly Lys Ala Gly Arg Asn
50 55 60
Ala Leu Leu Ala Gly Ala Pro Ile Leu Cys Asp Ala Arg Met Val Ala
65 70 75 80
Glu Gly Ile Thr Arg Ser Arg Leu Pro Ala Asp Asn Arg Val Ile Tyr
85 90 95
Thr Leu Ser Asp Pro Ser Val Pro Glu Leu Ala Lys Lys Ile Gly Asn
100 105 110
Thr Arg Ser Ala Ala Ala Leu Asp Leu Trp Leu Pro His Ile Glu Gly
115 120 125
Ser Ile Val Ala Ile Gly Asn Ala Pro Thr Ala Leu Phe Arg Leu Phe
130 135 140
Glu Leu Leu Asp Ala Gly Ala Pro Lys Pro Ala Leu Ile Ile Gly Met
145 150 155 160
Pro Val Gly Phe Val Gly Ala Ala Glu Ser Lys Asp Glu Leu Ala Ala
165 170 175
Asn Ser Arg Gly Val Pro Tyr Val Ile Val Arg Gly Arg Arg Gly Gly
180 185 190
Ser Ala Met Thr Ala Ala Ala Val Asn Ala Leu Ala Ser Glu Arg Glu
195 200 205
<210> 18
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> I32-06B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 18
Met Ile Thr Val Phe Gly Leu Lys Ser Lys Leu Ala Pro Arg Arg Glu
1 5 10 15
Lys Leu Ala Glu Val Ile Tyr Ser Ser Leu His Leu Gly Leu Asp Ile
20 25 30
Pro Lys Gly Lys His Ala Ile Arg Phe Leu Cys Leu Glu Lys Glu Asp
35 40 45
Phe Tyr Tyr Pro Phe Asp Arg Ser Asp Asp Tyr Thr Val Ile Glu Ile
50 55 60
Asn Leu Met Ala Gly Arg Ser Glu Glu Thr Lys Met Leu Leu Ile Phe
65 70 75 80
Leu Leu Phe Ile Ala Leu Glu Arg Lys Leu Gly Ile Arg Ala His Asp
85 90 95
Val Glu Ile Thr Ile Lys Glu Gln Pro Ala His Cys Trp Gly Phe Arg
100 105 110
Gly Arg Thr Gly Asp Ser Ala Arg Asp Leu Asp Tyr Asp Ile Tyr Val
115 120 125
<210> 19
<211> 235
<212> PRT
<213> 人工序列
<220>
<223> I32-19A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 19
Met Gly Ser Asp Leu Gln Lys Leu Gln Arg Phe Ser Thr Cys Asp Ile
1 5 10 15
Ser Asp Gly Leu Leu Asn Val Tyr Asn Ile Pro Thr Gly Gly Tyr Phe
20 25 30
Pro Asn Leu Thr Ala Ile Ser Pro Pro Gln Asn Ser Ser Ile Val Gly
35 40 45
Thr Ala Tyr Thr Val Leu Phe Ala Pro Ile Asp Asp Pro Arg Pro Ala
50 55 60
Val Asn Tyr Ile Asp Ser Val Pro Pro Asn Ser Ile Leu Val Leu Ala
65 70 75 80
Leu Glu Pro His Leu Gln Ser Gln Phe His Pro Phe Ile Lys Ile Thr
85 90 95
Gln Ala Met Tyr Gly Gly Leu Met Ser Thr Arg Ala Gln Tyr Leu Lys
100 105 110
Ser Asn Gly Thr Val Val Phe Gly Arg Ile Arg Asp Val Asp Glu His
115 120 125
Arg Thr Leu Asn His Pro Val Phe Ala Tyr Gly Val Gly Ser Cys Ala
130 135 140
Pro Lys Ala Val Val Lys Ala Val Gly Thr Asn Val Gln Leu Lys Ile
145 150 155 160
Leu Thr Ser Asp Gly Val Thr Gln Thr Ile Cys Pro Gly Asp Tyr Ile
165 170 175
Ala Gly Asp Asn Asn Gly Ile Val Arg Ile Pro Val Gln Glu Thr Asp
180 185 190
Ile Ser Lys Leu Val Thr Tyr Ile Glu Lys Ser Ile Glu Val Asp Arg
195 200 205
Leu Val Ser Glu Ala Ile Lys Asn Gly Leu Pro Ala Lys Ala Ala Gln
210 215 220
Thr Ala Arg Arg Met Val Leu Lys Asp Tyr Ile
225 230 235
<210> 20
<211> 162
<212> PRT
<213> 人工序列
<220>
<223> I32-19B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 20
Met Ser Gly Met Arg Val Tyr Leu Gly Ala Asp His Ala Gly Tyr Glu
1 5 10 15
Leu Lys Gln Ala Ile Ile Ala Phe Leu Lys Met Thr Gly His Glu Pro
20 25 30
Ile Asp Cys Gly Ala Leu Arg Tyr Asp Ala Asp Asp Asp Tyr Pro Ala
35 40 45
Phe Cys Ile Ala Ala Ala Thr Arg Thr Val Ala Asp Pro Gly Ser Leu
50 55 60
Gly Ile Val Leu Gly Gly Ser Gly Asn Gly Glu Gln Ile Ala Ala Asn
65 70 75 80
Lys Val Pro Gly Ala Arg Cys Ala Leu Ala Trp Ser Val Gln Thr Ala
85 90 95
Ala Leu Ala Arg Glu His Asn Asn Ala Gln Leu Ile Gly Ile Gly Gly
100 105 110
Arg Met His Thr Leu Glu Glu Ala Leu Arg Ile Val Lys Ala Phe Val
115 120 125
Thr Thr Pro Trp Ser Lys Ala Gln Arg His Gln Arg Arg Ile Asp Ile
130 135 140
Leu Ala Glu Tyr Glu Arg Thr His Glu Ala Pro Pro Val Pro Gly Ala
145 150 155 160
Pro Ala
<210> 21
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I32-28A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 21
Met Gly Asp Asp Ala Arg Ile Ala Ala Ile Gly Asp Val Asp Glu Leu
1 5 10 15
Asn Ser Gln Ile Gly Val Leu Leu Ala Glu Pro Leu Pro Asp Asp Val
20 25 30
Arg Ala Ala Leu Ser Ala Ile Gln His Asp Leu Phe Asp Leu Gly Gly
35 40 45
Glu Leu Cys Ile Pro Gly His Ala Ala Ile Thr Glu Asp His Leu Leu
50 55 60
Arg Leu Ala Leu Trp Leu Val His Tyr Asn Gly Gln Leu Pro Pro Leu
65 70 75 80
Glu Glu Phe Ile Leu Pro Gly Gly Ala Arg Gly Ala Ala Leu Ala His
85 90 95
Val Cys Arg Thr Val Cys Arg Arg Ala Glu Arg Ser Ile Lys Ala Leu
100 105 110
Gly Ala Ser Glu Pro Leu Asn Ile Ala Pro Ala Ala Tyr Val Asn Leu
115 120 125
Leu Ser Asp Leu Leu Phe Val Leu Ala Arg Val Leu Asn Arg Ala Ala
130 135 140
Gly Gly Ala Asp Val Leu Trp Asp Arg Thr Arg Ala His
145 150 155
<210> 22
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I32-28B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 22
Met Ile Leu Ser Ala Glu Gln Ser Phe Thr Leu Arg His Pro His Gly
1 5 10 15
Gln Ala Ala Ala Leu Ala Phe Val Arg Glu Pro Ala Ala Ala Leu Ala
20 25 30
Gly Val Gln Arg Leu Arg Gly Leu Asp Ser Asp Gly Glu Gln Val Trp
35 40 45
Gly Glu Leu Leu Val Arg Val Pro Leu Leu Gly Glu Val Asp Leu Pro
50 55 60
Phe Arg Ser Glu Ile Val Arg Thr Pro Gln Gly Ala Glu Leu Arg Pro
65 70 75 80
Leu Thr Leu Thr Gly Glu Arg Ala Trp Val Ala Val Ser Gly Gln Ala
85 90 95
Thr Ala Ala Glu Gly Gly Glu Met Ala Phe Ala Phe Gln Phe Gln Ala
100 105 110
His Leu Ala Thr Pro Glu Ala Glu Gly Glu Gly Gly Ala Ala Phe Glu
115 120 125
Val Met Val Gln Ala Ala Ala Gly Val Thr Leu Leu Leu Val Ala Met
130 135 140
Ala Leu Pro Gln Gly Leu Ala Ala Gly Leu Pro Pro Ala
145 150 155
<210> 23
<211> 156
<212> PRT
<213> 人工序列
<220>
<223> I53-40A.1
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 23
Met Thr Lys Lys Val Gly Ile Val Asp Thr Thr Phe Ala Arg Val Asp
1 5 10 15
Met Ala Ser Ala Ala Ile Leu Thr Leu Lys Met Glu Ser Pro Asn Ile
20 25 30
Lys Ile Ile Arg Lys Thr Val Pro Gly Ile Lys Asp Leu Pro Val Ala
35 40 45
Cys Lys Lys Leu Leu Glu Glu Glu Gly Cys Asp Ile Val Met Ala Leu
50 55 60
Gly Met Pro Gly Lys Lys Glu Lys Asp Lys Val Cys Ala His Glu Ala
65 70 75 80
Ser Leu Gly Leu Met Leu Ala Gln Leu Met Thr Asn Lys His Ile Ile
85 90 95
Glu Val Phe Val His Glu Asp Glu Ala Lys Asp Asp Ala Glu Leu Lys
100 105 110
Ile Leu Ala Ala Arg Arg Ala Ile Glu His Ala Leu Asn Val Tyr Tyr
115 120 125
Leu Leu Phe Lys Pro Glu Tyr Leu Thr Arg Met Ala Gly Lys Gly Leu
130 135 140
Arg Gln Gly Phe Glu Asp Ala Gly Pro Ala Arg Glu
145 150 155
<210> 24
<211> 209
<212> PRT
<213> 人工序列
<220>
<223> I53-40B.1
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 24
Met Asp Asp Ile Asn Asn Gln Leu Lys Arg Leu Lys Val Ile Pro Val
1 5 10 15
Ile Ala Ile Asp Asn Ala Glu Asp Ile Ile Pro Leu Gly Lys Val Leu
20 25 30
Ala Glu Asn Gly Leu Pro Ala Ala Glu Ile Thr Phe Arg Ser Ser Ala
35 40 45
Ala Val Lys Ala Ile Met Leu Leu Arg Ser Ala Gln Pro Glu Met Leu
50 55 60
Ile Gly Ala Gly Thr Ile Leu Asn Gly Val Gln Ala Leu Ala Ala Lys
65 70 75 80
Glu Ala Gly Ala Asp Phe Val Val Ser Pro Gly Phe Asn Pro Asn Thr
85 90 95
Val Arg Ala Cys Gln Ile Ile Gly Ile Asp Ile Val Pro Gly Val Asn
100 105 110
Asn Pro Ser Thr Val Glu Gln Ala Leu Glu Met Gly Leu Thr Thr Leu
115 120 125
Lys Phe Phe Pro Ala Glu Ala Ser Gly Gly Ile Ser Met Val Lys Ser
130 135 140
Leu Val Gly Pro Tyr Gly Asp Ile Arg Leu Met Pro Thr Gly Gly Ile
145 150 155 160
Thr Pro Asp Asn Ile Asp Asn Tyr Leu Ala Ile Pro Gln Val Leu Ala
165 170 175
Cys Gly Gly Thr Trp Met Val Asp Lys Lys Leu Val Arg Asn Gly Glu
180 185 190
Trp Asp Glu Ile Ala Arg Leu Thr Arg Glu Ile Val Glu Gln Val Asn
195 200 205
Pro
<210> 25
<211> 114
<212> PRT
<213> 人工序列
<220>
<223> I53-47A.1
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 25
Met Pro Ile Phe Thr Leu Asn Thr Asn Ile Lys Ala Asp Asp Val Pro
1 5 10 15
Ser Asp Phe Leu Ser Leu Thr Ser Arg Leu Val Gly Leu Ile Leu Ser
20 25 30
Lys Pro Gly Ser Tyr Val Ala Val His Ile Asn Thr Asp Gln Gln Leu
35 40 45
Ser Phe Gly Gly Ser Thr Asn Pro Ala Ala Phe Gly Thr Leu Met Ser
50 55 60
Ile Gly Gly Ile Glu Pro Asp Lys Asn Arg Asp His Ser Ala Val Leu
65 70 75 80
Phe Asp His Leu Asn Ala Met Leu Gly Ile Pro Lys Asn Arg Met Tyr
85 90 95
Ile His Phe Val Asn Leu Asn Gly Asp Asp Val Gly Trp Asn Gly Thr
100 105 110
Thr Phe
<210> 26
<211> 114
<212> PRT
<213> 人工序列
<220>
<223> I53-47A.1NegT2
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 26
Met Pro Ile Phe Thr Leu Asn Thr Asn Ile Lys Ala Asp Asp Val Pro
1 5 10 15
Ser Asp Phe Leu Ser Leu Thr Ser Arg Leu Val Gly Leu Ile Leu Ser
20 25 30
Glu Pro Gly Ser Tyr Val Ala Val His Ile Asn Thr Asp Gln Gln Leu
35 40 45
Ser Phe Gly Gly Ser Thr Asn Pro Ala Ala Phe Gly Thr Leu Met Ser
50 55 60
Ile Gly Gly Ile Glu Pro Asp Lys Asn Glu Asp His Ser Ala Val Leu
65 70 75 80
Phe Asp His Leu Asn Ala Met Leu Gly Ile Pro Lys Asn Arg Met Tyr
85 90 95
Ile His Phe Val Asp Leu Asp Gly Asp Asp Val Gly Trp Asn Gly Thr
100 105 110
Thr Phe
<210> 27
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-47B.1
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 27
Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Asp Ile Val Asp Ala Cys Val Glu Ala
20 25 30
Phe Glu Ile Ala Met Ala Ala Ile Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Arg Tyr Arg Asp Ser Asp Glu His His Arg
115 120 125
Phe Phe Ala Ala His Phe Ala Val Lys Gly Val Glu Ala Ala Arg Ala
130 135 140
Cys Ile Glu Ile Leu Asn Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 28
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-47B.1NegT2
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 28
Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Asp Ile Val Asp Ala Cys Val Glu Ala
20 25 30
Phe Glu Ile Ala Met Ala Ala Ile Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Asp Gly Gly Ile Tyr Asp His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Glu Tyr Glu Asp Ser Asp Glu Asp His Glu
115 120 125
Phe Phe Ala Ala His Phe Ala Val Lys Gly Val Glu Ala Ala Arg Ala
130 135 140
Cys Ile Glu Ile Leu Asn Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 29
<211> 205
<212> PRT
<213> 人工序列
<220>
<223> I53-50A.1
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 29
Met Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu
1 5 10 15
Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe
20 25 30
Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala
35 40 45
Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile
50 55 60
Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val
65 70 75 80
Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile
85 90 95
Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met
100 105 110
Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Asp Ile Leu
115 120 125
Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met
130 135 140
Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn
145 150 155 160
Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly
165 170 175
Val Gly Asp Ala Leu Val Lys Gly Asp Pro Asp Glu Val Arg Glu Lys
180 185 190
Ala Lys Lys Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
195 200 205
<210> 30
<211> 205
<212> PRT
<213> 人工序列
<220>
<223> I53-50A.1NegT2
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 30
Met Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu
1 5 10 15
Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe
20 25 30
Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala
35 40 45
Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile
50 55 60
Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val
65 70 75 80
Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile
85 90 95
Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met
100 105 110
Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Asp Ile Leu
115 120 125
Lys Leu Phe Pro Gly Glu Val Val Gly Pro Glu Phe Val Glu Ala Met
130 135 140
Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asp
145 150 155 160
Leu Asp Asp Val Cys Glu Trp Phe Asp Ala Gly Val Leu Ala Val Gly
165 170 175
Val Gly Asp Ala Leu Val Glu Gly Asp Pro Asp Glu Val Arg Glu Asp
180 185 190
Ala Lys Glu Phe Val Glu Glu Ile Arg Gly Cys Thr Glu
195 200 205
<210> 31
<211> 205
<212> PRT
<213> 人工序列
<220>
<223> I53-50A.1PosT1
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 31
Met Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu
1 5 10 15
Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe
20 25 30
Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala
35 40 45
Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile
50 55 60
Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val
65 70 75 80
Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile
85 90 95
Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met
100 105 110
Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Asp Ile Leu
115 120 125
Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met
130 135 140
Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn
145 150 155 160
Leu Asp Asn Val Cys Lys Trp Phe Lys Ala Gly Val Leu Ala Val Gly
165 170 175
Val Gly Lys Ala Leu Val Lys Gly Lys Pro Asp Glu Val Arg Glu Lys
180 185 190
Ala Lys Lys Phe Val Lys Lys Ile Arg Gly Cys Thr Glu
195 200 205
<210> 32
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-50B.1
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 32
Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala
20 25 30
Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Arg Tyr Arg Asp Ser Asp Ala His Thr Leu
115 120 125
Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala
130 135 140
Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 33
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-50B.1NegT2
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 33
Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala
20 25 30
Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Asp Gly Gly Ile Tyr Asp His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Glu Tyr Glu Asp Ser Asp Ala Asp Thr Leu
115 120 125
Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala
130 135 140
Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 34
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-50B.4PosT1
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 34
Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala
20 25 30
Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Asn Gly Met Met Asn Val Gln Leu Asn Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Asn Tyr Asp Lys Ser Lys Ala His Thr Leu
115 120 125
Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala
130 135 140
Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 35
<211> 156
<212> PRT
<213> 人工序列
<220>
<223> I53-40 A属
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (70)..(70)
<223> Xaa为A 或K
<400> 35
Met Thr Lys Lys Val Gly Ile Val Asp Thr Thr Phe Ala Arg Val Asp
1 5 10 15
Met Ala Ser Ala Ala Ile Leu Thr Leu Lys Met Glu Ser Pro Asn Ile
20 25 30
Lys Ile Ile Arg Lys Thr Val Pro Gly Ile Lys Asp Leu Pro Val Ala
35 40 45
Cys Lys Lys Leu Leu Glu Glu Glu Gly Cys Asp Ile Val Met Ala Leu
50 55 60
Gly Met Pro Gly Lys Xaa Glu Lys Asp Lys Val Cys Ala His Glu Ala
65 70 75 80
Ser Leu Gly Leu Met Leu Ala Gln Leu Met Thr Asn Lys His Ile Ile
85 90 95
Glu Val Phe Val His Glu Asp Glu Ala Lys Asp Asp Ala Glu Leu Lys
100 105 110
Ile Leu Ala Ala Arg Arg Ala Ile Glu His Ala Leu Asn Val Tyr Tyr
115 120 125
Leu Leu Phe Lys Pro Glu Tyr Leu Thr Arg Met Ala Gly Lys Gly Leu
130 135 140
Arg Gln Gly Phe Glu Asp Ala Gly Pro Ala Arg Glu
145 150 155
<210> 36
<211> 209
<212> PRT
<213> 人工序列
<220>
<223> I53-40 B属
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (2)..(2)
<223> Xaa为S或D
<220>
<221> 尚未归类的特征
<222> (3)..(3)
<223> Xaa为T或D
<220>
<221> 尚未归类的特征
<222> (10)..(10)
<223> Xaa为A或R
<220>
<221> 尚未归类的特征
<222> (85)..(85)
<223> Xaa为T或D
<220>
<221> 尚未归类的特征
<222> (119)..(119)
<223> Xaa为A或Q
<220>
<221> 尚未归类的特征
<222> (163)..(163)
<223> Xaa为S或D
<220>
<221> 尚未归类的特征
<222> (189)..(189)
<223> Xaa为T或R
<400> 36
Met Xaa Xaa Ile Asn Asn Gln Leu Lys Xaa Leu Lys Val Ile Pro Val
1 5 10 15
Ile Ala Ile Asp Asn Ala Glu Asp Ile Ile Pro Leu Gly Lys Val Leu
20 25 30
Ala Glu Asn Gly Leu Pro Ala Ala Glu Ile Thr Phe Arg Ser Ser Ala
35 40 45
Ala Val Lys Ala Ile Met Leu Leu Arg Ser Ala Gln Pro Glu Met Leu
50 55 60
Ile Gly Ala Gly Thr Ile Leu Asn Gly Val Gln Ala Leu Ala Ala Lys
65 70 75 80
Glu Ala Gly Ala Xaa Phe Val Val Ser Pro Gly Phe Asn Pro Asn Thr
85 90 95
Val Arg Ala Cys Gln Ile Ile Gly Ile Asp Ile Val Pro Gly Val Asn
100 105 110
Asn Pro Ser Thr Val Glu Xaa Ala Leu Glu Met Gly Leu Thr Thr Leu
115 120 125
Lys Phe Phe Pro Ala Glu Ala Ser Gly Gly Ile Ser Met Val Lys Ser
130 135 140
Leu Val Gly Pro Tyr Gly Asp Ile Arg Leu Met Pro Thr Gly Gly Ile
145 150 155 160
Thr Pro Xaa Asn Ile Asp Asn Tyr Leu Ala Ile Pro Gln Val Leu Ala
165 170 175
Cys Gly Gly Thr Trp Met Val Asp Lys Lys Leu Val Xaa Asn Gly Glu
180 185 190
Trp Asp Glu Ile Ala Arg Leu Thr Arg Glu Ile Val Glu Gln Val Asn
195 200 205
Pro
<210> 37
<211> 114
<212> PRT
<213> 人工序列
<220>
<223> I53-47A属
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (13)..(13)
<223> Xaa为T或D
<220>
<221> 尚未归类的特征
<222> (33)..(33)
<223> Xaa为K或E
<220>
<221> 尚未归类的特征
<222> (71)..(71)
<223> Xaa为S或D
<220>
<221> 尚未归类的特征
<222> (74)..(74)
<223> Xaa为R或E
<220>
<221> 尚未归类的特征
<222> (101)..(101)
<223> Xaa为N或D
<220>
<221> 尚未归类的特征
<222> (103)..(103)
<223> Xaa为N或D
<400> 37
Met Pro Ile Phe Thr Leu Asn Thr Asn Ile Lys Ala Xaa Asp Val Pro
1 5 10 15
Ser Asp Phe Leu Ser Leu Thr Ser Arg Leu Val Gly Leu Ile Leu Ser
20 25 30
Xaa Pro Gly Ser Tyr Val Ala Val His Ile Asn Thr Asp Gln Gln Leu
35 40 45
Ser Phe Gly Gly Ser Thr Asn Pro Ala Ala Phe Gly Thr Leu Met Ser
50 55 60
Ile Gly Gly Ile Glu Pro Xaa Lys Asn Xaa Asp His Ser Ala Val Leu
65 70 75 80
Phe Asp His Leu Asn Ala Met Leu Gly Ile Pro Lys Asn Arg Met Tyr
85 90 95
Ile His Phe Val Xaa Leu Xaa Gly Asp Asp Val Gly Trp Asn Gly Thr
100 105 110
Thr Phe
<210> 38
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-47B属
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (9)..(9)
<223> Xaa为Y或H
<220>
<221> 尚未归类的特征
<222> (82)..(82)
<223> Xaa为N或D
<220>
<221> 尚未归类的特征
<222> (87)..(87)
<223> Xaa为R或D
<220>
<221> 尚未归类的特征
<222> (105)..(105)
<223> Xaa为S或D
<220>
<221> 尚未归类的特征
<222> (119)..(119)
<223> Xaa为R或E
<220>
<221> 尚未归类的特征
<222> (121)..(121)
<223> Xaa为R或E
<220>
<221> 尚未归类的特征
<222> (124)..(124)
<223> Xaa为A或D
<220>
<221> 尚未归类的特征
<222> (126)..(126)
<223> Xaa为H或D
<220>
<221> 尚未归类的特征
<222> (128)..(128)
<223> Xaa为R或E
<220>
<221> 尚未归类的特征
<222> (150)..(150)
<223> Xaa为A或N
<400> 38
Met Asn Gln His Ser His Lys Asp Xaa Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Asp Ile Val Asp Ala Cys Val Glu Ala
20 25 30
Phe Glu Ile Ala Met Ala Ala Ile Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Xaa Gly Gly Ile Tyr Xaa His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Asp Gly Met Met Asn Val Gln Leu Xaa Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Xaa Tyr Xaa Asp Ser Xaa Glu Xaa His Xaa
115 120 125
Phe Phe Ala Ala His Phe Ala Val Lys Gly Val Glu Ala Ala Arg Ala
130 135 140
Cys Ile Glu Ile Leu Xaa Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 39
<211> 205
<212> PRT
<213> 人工序列
<220>
<223> I53-50A属
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (126)..(126)
<223> Xaa为T或D
<220>
<221> 尚未归类的特征
<222> (139)..(139)
<223> Xaa为Q或E
<220>
<221> 尚未归类的特征
<222> (142)..(142)
<223> Xaa为K或E
<220>
<221> 尚未归类的特征
<222> (160)..(160)
<223> Xaa为N或D
<220>
<221> 尚未归类的特征
<222> (163)..(163)
<223> Xaa为N或D
<220>
<221> 尚未归类的特征
<222> (166)..(166)
<223> Xaa为E或K
<220>
<221> 尚未归类的特征
<222> (169)..(169)
<223> Xaa为D或K
<220>
<221> 尚未归类的特征
<222> (179)..(179)
<223> Xaa为S, D或K
<220>
<221> 尚未归类的特征
<222> (183)..(183)
<223> Xaa为K或E
<220>
<221> 尚未归类的特征
<222> (185)..(185)
<223> Xaa为T, D或K
<220>
<221> 尚未归类的特征
<222> (192)..(192)
<223> Xaa为D或K
<220>
<221> 尚未归类的特征
<222> (195)..(195)
<223> Xaa为A, E或K
<220>
<221> 尚未归类的特征
<222> (198)..(198)
<223> Xaa为E或K
<220>
<221> 尚未归类的特征
<222> (199)..(199)
<223> Xaa为E或K
<400> 39
Met Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu
1 5 10 15
Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe
20 25 30
Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala
35 40 45
Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile
50 55 60
Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val
65 70 75 80
Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile
85 90 95
Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met
100 105 110
Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Xaa Ile Leu
115 120 125
Lys Leu Phe Pro Gly Glu Val Val Gly Pro Xaa Phe Val Xaa Ala Met
130 135 140
Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Xaa
145 150 155 160
Leu Asp Xaa Val Cys Xaa Trp Phe Xaa Ala Gly Val Leu Ala Val Gly
165 170 175
Val Gly Xaa Ala Leu Val Xaa Gly Xaa Pro Asp Glu Val Arg Glu Xaa
180 185 190
Ala Lys Xaa Phe Val Xaa Xaa Ile Arg Gly Cys Thr Glu
195 200 205
<210> 40
<211> 157
<212> PRT
<213> 人工序列
<220>
<223> I53-50B属
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (9)..(9)
<223> Xaa为Y或H
<220>
<221> 尚未归类的特征
<222> (38)..(38)
<223> Xaa为A或R
<220>
<221> 尚未归类的特征
<222> (82)..(82)
<223> Xaa为N或D
<220>
<221> 尚未归类的特征
<222> (87)..(87)
<223> Xaa为R或D
<220>
<221> 尚未归类的特征
<222> (97)..(97)
<223> Xaa为N或D
<220>
<221> 尚未归类的特征
<222> (105)..(105)
<223> Xaa为S, N或D
<220>
<221> 尚未归类的特征
<222> (119)..(119)
<223> Xaa为R, E或N
<220>
<221> 尚未归类的特征
<222> (121)..(121)
<223> Xaa为R, E或D
<220>
<221> 尚未归类的特征
<222> (122)..(122)
<223> Xaa为K或D
<220>
<221> 尚未归类的特征
<222> (124)..(124)
<223> Xaa为K或D
<220>
<221> 尚未归类的特征
<222> (126)..(126)
<223> Xaa为H或D
<400> 40
Met Asn Gln His Ser His Lys Asp Xaa Glu Thr Val Arg Ile Ala Val
1 5 10 15
Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala
20 25 30
Phe Glu Ala Ala Met Xaa Asp Ile Gly Gly Asp Arg Phe Ala Val Asp
35 40 45
Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr
50 55 60
Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val
65 70 75 80
Val Xaa Gly Gly Ile Tyr Xaa His Glu Phe Val Ala Ser Ala Val Ile
85 90 95
Xaa Gly Met Met Asn Val Gln Leu Xaa Thr Gly Val Pro Val Leu Ser
100 105 110
Ala Val Leu Thr Pro His Xaa Tyr Xaa Xaa Ser Xaa Ala Xaa Thr Leu
115 120 125
Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala
130 135 140
Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala
145 150 155
<210> 41
<211> 159
<212> PRT
<213> 人工序列
<220>
<223> T32-28A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 41
Met Gly Glu Val Pro Ile Gly Asp Pro Lys Glu Leu Asn Gly Met Glu
1 5 10 15
Ile Ala Ala Val Tyr Leu Gln Pro Ile Glu Met Glu Pro Arg Gly Ile
20 25 30
Asp Leu Ala Ala Ser Leu Ala Asp Ile His Leu Glu Ala Asp Ile His
35 40 45
Ala Leu Lys Asn Asn Pro Asn Gly Phe Pro Glu Gly Phe Trp Met Pro
50 55 60
Tyr Leu Thr Ile Ala Tyr Ala Leu Ala Asn Ala Asp Thr Gly Ala Ile
65 70 75 80
Lys Thr Gly Thr Leu Met Pro Met Val Ala Asp Asp Gly Pro His Tyr
85 90 95
Gly Ala Asn Ile Ala Met Glu Lys Asp Lys Lys Gly Gly Phe Gly Val
100 105 110
Gly Thr Tyr Ala Leu Thr Phe Leu Ile Ser Asn Pro Glu Lys Gln Gly
115 120 125
Phe Gly Arg His Val Asp Glu Glu Thr Gly Val Gly Lys Trp Phe Glu
130 135 140
Pro Phe Val Val Thr Tyr Phe Phe Lys Tyr Thr Gly Thr Pro Lys
145 150 155
<210> 42
<211> 184
<212> PRT
<213> 人工序列
<220>
<223> T32-28B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 42
Met Ser Gln Ala Ile Gly Ile Leu Glu Leu Thr Ser Ile Ala Lys Gly
1 5 10 15
Met Glu Leu Gly Asp Ala Met Leu Lys Ser Ala Asn Val Asp Leu Leu
20 25 30
Val Ser Lys Thr Ile Ser Pro Gly Lys Phe Leu Leu Met Leu Gly Gly
35 40 45
Asp Ile Gly Ala Ile Gln Gln Ala Ile Glu Thr Gly Thr Ser Gln Ala
50 55 60
Gly Glu Met Leu Val Asp Ser Leu Val Leu Ala Asn Ile His Pro Ser
65 70 75 80
Val Leu Pro Ala Ile Ser Gly Leu Asn Ser Val Asp Lys Arg Gln Ala
85 90 95
Val Gly Ile Val Glu Thr Trp Ser Val Ala Ala Cys Ile Ser Ala Ala
100 105 110
Asp Leu Ala Val Lys Gly Ser Asn Val Thr Leu Val Arg Val His Met
115 120 125
Ala Phe Gly Ile Gly Gly Lys Cys Tyr Met Val Val Ala Gly Asp Val
130 135 140
Leu Asp Val Ala Ala Ala Val Ala Thr Ala Ser Leu Ala Ala Gly Ala
145 150 155 160
Lys Gly Leu Leu Val Tyr Ala Ser Ile Ile Pro Arg Pro His Glu Ala
165 170 175
Met Trp Arg Gln Met Val Glu Gly
180
<210> 43
<211> 103
<212> PRT
<213> 人工序列
<220>
<223> T33-09A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 43
Met Glu Glu Val Val Leu Ile Thr Val Pro Ser Ala Leu Val Ala Val
1 5 10 15
Lys Ile Ala His Ala Leu Val Glu Glu Arg Leu Ala Ala Cys Val Asn
20 25 30
Ile Val Pro Gly Leu Thr Ser Ile Tyr Arg Trp Gln Gly Ser Val Val
35 40 45
Ser Asp His Glu Leu Leu Leu Leu Val Lys Thr Thr Thr His Ala Phe
50 55 60
Pro Lys Leu Lys Glu Arg Val Lys Ala Leu His Pro Tyr Thr Val Pro
65 70 75 80
Glu Ile Val Ala Leu Pro Ile Ala Glu Gly Asn Arg Glu Tyr Leu Asp
85 90 95
Trp Leu Arg Glu Asn Thr Gly
100
<210> 44
<211> 122
<212> PRT
<213> 人工序列
<220>
<223> T33-09B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 44
Met Val Arg Gly Ile Arg Gly Ala Ile Thr Val Glu Glu Asp Thr Pro
1 5 10 15
Ala Ala Ile Leu Ala Ala Thr Ile Glu Leu Leu Leu Lys Met Leu Glu
20 25 30
Ala Asn Gly Ile Gln Ser Tyr Glu Glu Leu Ala Ala Val Ile Phe Thr
35 40 45
Val Thr Glu Asp Leu Thr Ser Ala Phe Pro Ala Glu Ala Ala Arg Leu
50 55 60
Ile Gly Met His Arg Val Pro Leu Leu Ser Ala Arg Glu Val Pro Val
65 70 75 80
Pro Gly Ser Leu Pro Arg Val Ile Arg Val Leu Ala Leu Trp Asn Thr
85 90 95
Asp Thr Pro Gln Asp Arg Val Arg His Val Tyr Leu Asn Glu Ala Val
100 105 110
Arg Leu Arg Pro Asp Leu Glu Ser Ala Gln
115 120
<210> 45
<211> 177
<212> PRT
<213> 人工序列
<220>
<223> T33-15A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 45
Met Ser Lys Ala Lys Ile Gly Ile Val Thr Val Ser Asp Arg Ala Ser
1 5 10 15
Ala Gly Ile Thr Ala Asp Ile Ser Gly Lys Ala Ile Ile Leu Ala Leu
20 25 30
Asn Leu Tyr Leu Thr Ser Glu Trp Glu Pro Ile Tyr Gln Val Ile Pro
35 40 45
Asp Glu Gln Asp Val Ile Glu Thr Thr Leu Ile Lys Met Ala Asp Glu
50 55 60
Gln Asp Cys Cys Leu Ile Val Thr Thr Gly Gly Thr Gly Pro Ala Lys
65 70 75 80
Arg Asp Val Thr Pro Glu Ala Thr Glu Ala Val Cys Asp Arg Met Met
85 90 95
Pro Gly Phe Gly Glu Leu Met Arg Ala Glu Ser Leu Lys Glu Val Pro
100 105 110
Thr Ala Ile Leu Ser Arg Gln Thr Ala Gly Leu Arg Gly Asp Ser Leu
115 120 125
Ile Val Asn Leu Pro Gly Asp Pro Ala Ser Ile Ser Asp Cys Leu Leu
130 135 140
Ala Val Phe Pro Ala Ile Pro Tyr Cys Ile Asp Leu Met Glu Gly Pro
145 150 155 160
Tyr Leu Glu Cys Asn Glu Ala Met Ile Lys Pro Phe Arg Pro Lys Ala
165 170 175
Lys
<210> 46
<211> 122
<212> PRT
<213> 人工序列
<220>
<223> T33-15B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 46
Met Val Arg Gly Ile Arg Gly Ala Ile Thr Val Asn Ser Asp Thr Pro
1 5 10 15
Thr Ser Ile Ile Ile Ala Thr Ile Leu Leu Leu Glu Lys Met Leu Glu
20 25 30
Ala Asn Gly Ile Gln Ser Tyr Glu Glu Leu Ala Ala Val Ile Phe Thr
35 40 45
Val Thr Glu Asp Leu Thr Ser Ala Phe Pro Ala Glu Ala Ala Arg Gln
50 55 60
Ile Gly Met His Arg Val Pro Leu Leu Ser Ala Arg Glu Val Pro Val
65 70 75 80
Pro Gly Ser Leu Pro Arg Val Ile Arg Val Leu Ala Leu Trp Asn Thr
85 90 95
Asp Thr Pro Gln Asp Arg Val Arg His Val Tyr Leu Ser Glu Ala Val
100 105 110
Arg Leu Arg Pro Asp Leu Glu Ser Ala Gln
115 120
<210> 47
<211> 172
<212> PRT
<213> 人工序列
<220>
<223> T33-21A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 47
Met Arg Ile Thr Thr Lys Val Gly Asp Lys Gly Ser Thr Arg Leu Phe
1 5 10 15
Gly Gly Glu Glu Val Trp Lys Asp Ser Pro Ile Ile Glu Ala Asn Gly
20 25 30
Thr Leu Asp Glu Leu Thr Ser Phe Ile Gly Glu Ala Lys His Tyr Val
35 40 45
Asp Glu Glu Met Lys Gly Ile Leu Glu Glu Ile Gln Asn Asp Ile Tyr
50 55 60
Lys Ile Met Gly Glu Ile Gly Ser Lys Gly Lys Ile Glu Gly Ile Ser
65 70 75 80
Glu Glu Arg Ile Ala Trp Leu Leu Lys Leu Ile Leu Arg Tyr Met Glu
85 90 95
Met Val Asn Leu Lys Ser Phe Val Leu Pro Gly Gly Thr Leu Glu Ser
100 105 110
Ala Lys Leu Asp Val Cys Arg Thr Ile Ala Arg Arg Ala Leu Arg Lys
115 120 125
Val Leu Thr Val Thr Arg Glu Phe Gly Ile Gly Ala Glu Ala Ala Ala
130 135 140
Tyr Leu Leu Ala Leu Ser Asp Leu Leu Phe Leu Leu Ala Arg Val Ile
145 150 155 160
Glu Ile Glu Lys Asn Lys Leu Lys Glu Val Arg Ser
165 170
<210> 48
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> T33-21B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 48
Met Pro His Leu Val Ile Glu Ala Thr Ala Asn Leu Arg Leu Glu Thr
1 5 10 15
Ser Pro Gly Glu Leu Leu Glu Gln Ala Asn Lys Ala Leu Phe Ala Ser
20 25 30
Gly Gln Phe Gly Glu Ala Asp Ile Lys Ser Arg Phe Val Thr Leu Glu
35 40 45
Ala Tyr Arg Gln Gly Thr Ala Ala Val Glu Arg Ala Tyr Leu His Ala
50 55 60
Cys Leu Ser Ile Leu Asp Gly Arg Asp Ile Ala Thr Arg Thr Leu Leu
65 70 75 80
Gly Ala Ser Leu Cys Ala Val Leu Ala Glu Ala Val Ala Gly Gly Gly
85 90 95
Glu Glu Gly Val Gln Val Ser Val Glu Val Arg Glu Met Glu Arg Leu
100 105 110
Ser Tyr Ala Lys Arg Val Val Ala Arg Gln Arg
115 120
<210> 49
<211> 158
<212> PRT
<213> 人工序列
<220>
<223> T33-28A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 49
Met Glu Ser Val Asn Thr Ser Phe Leu Ser Pro Ser Leu Val Thr Ile
1 5 10 15
Arg Asp Phe Asp Asn Gly Gln Phe Ala Val Leu Arg Ile Gly Arg Thr
20 25 30
Gly Phe Pro Ala Asp Lys Gly Asp Ile Asp Leu Cys Leu Asp Lys Met
35 40 45
Ile Gly Val Arg Ala Ala Gln Ile Phe Leu Gly Asp Asp Thr Glu Asp
50 55 60
Gly Phe Lys Gly Pro His Ile Arg Ile Arg Cys Val Asp Ile Asp Asp
65 70 75 80
Lys His Thr Tyr Asn Ala Met Val Tyr Val Asp Leu Ile Val Gly Thr
85 90 95
Gly Ala Ser Glu Val Glu Arg Glu Thr Ala Glu Glu Glu Ala Lys Leu
100 105 110
Ala Leu Arg Val Ala Leu Gln Val Asp Ile Ala Asp Glu His Ser Cys
115 120 125
Val Thr Gln Phe Glu Met Lys Leu Arg Glu Glu Leu Leu Ser Ser Asp
130 135 140
Ser Phe His Pro Asp Lys Asp Glu Tyr Tyr Lys Asp Phe Leu
145 150 155
<210> 50
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> T33-28B
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 50
Met Pro Val Ile Gln Thr Phe Val Ser Thr Pro Leu Asp His His Lys
1 5 10 15
Arg Leu Leu Leu Ala Ile Ile Tyr Arg Ile Val Thr Arg Val Val Leu
20 25 30
Gly Lys Pro Glu Asp Leu Val Met Met Thr Phe His Asp Ser Thr Pro
35 40 45
Met His Phe Phe Gly Ser Thr Asp Pro Val Ala Cys Val Arg Val Glu
50 55 60
Ala Leu Gly Gly Tyr Gly Pro Ser Glu Pro Glu Lys Val Thr Ser Ile
65 70 75 80
Val Thr Ala Ala Ile Thr Ala Val Cys Gly Ile Val Ala Asp Arg Ile
85 90 95
Phe Val Leu Tyr Phe Ser Pro Leu His Cys Gly Trp Asn Gly Thr Asn
100 105 110
Phe
<210> 51
<211> 103
<212> PRT
<213> 人工序列
<220>
<223> T33-31A
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> 可选地不存在
<400> 51
Met Glu Glu Val Val Leu Ile Thr Val Pro Ser Ala Leu Val Ala Val
1 5 10 15
Lys Ile Ala His Ala Leu Val Glu Glu Arg Leu Ala Ala Cys Val Asn
20 25 30
Ile Val Pro Gly Leu Thr Ser Ile Tyr Arg Glu Glu Gly Ser Val Val
35 40 45
Ser Asp His Glu Leu Leu Leu Leu Val Lys Thr Thr Thr Asp Ala Phe
50 55 60
Pro Lys Leu Lys Glu Arg Val Lys Glu Leu His Pro Tyr Glu Val Pro
65 70 75 80
Glu Ile Val Ala Leu Pro Ile Ala Glu Gly Asn Arg Glu Tyr Leu Asp
85 90 95
Trp Leu Arg Glu Asn Thr Gly
100
<210> 52
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成肽
<400> 52
Gln Asn Ile Thr Glu Glu Phe
1 5
<210> 53
<211> 513
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (508)..(513)
<223> 可选地不存在
<400> 53
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu
<210> 54
<211> 27
<212> PRT
<213> 人工序列
<220>
<223> T4纤维蛋白折叠结构域
<400> 54
Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys
1 5 10 15
Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
20 25
<210> 55
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 接头
<400> 55
Gly Ser Gly Gly Ser Gly Ser Gly Ser Gly Gly Ser Gly Ser Gly
1 5 10 15
<210> 56
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 接头
<400> 56
Gly Gly Ser Gly Gly Ser Gly Ser
1 5
<210> 57
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 接头
<400> 57
Gly Ser Gly Gly Ser Gly Ser Gly
1 5
<210> 58
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 螺旋延伸
<400> 58
Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg
1 5 10
<210> 59
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 信号肽
<400> 59
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly
20 25
<210> 60
<211> 540
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-折叠子
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 60
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg
515 520 525
Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
<210> 61
<211> 474
<212> PRT
<213> 人工序列
<220>
<223> sc9-10 DS-Cav1 A149C Y458C
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (468)..(474)
<223> 可选地不存在
<400> 61
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Gly Ser Gly Ser Ala Ile Cys Ser Gly
100 105 110
Val Ala Val Cys Lys Val Leu His Leu Glu Gly Glu Val Asn Lys Ile
115 120 125
Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser Asn
130 135 140
Gly Val Ser Val Leu Thr Phe Lys Val Leu Asp Leu Lys Asn Tyr Ile
145 150 155 160
Asp Lys Gln Leu Leu Pro Ile Leu Asn Lys Gln Ser Cys Ser Ile Ser
165 170 175
Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu Leu
180 185 190
Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro Val
195 200 205
Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn Asp
210 215 220
Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val Gln
225 230 235 240
Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Cys Ile Ile Lys Glu Glu
245 250 255
Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp Thr
260 265 270
Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr Lys
275 280 285
Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr Cys
290 295 300
Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys Lys
305 310 315 320
Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Arg Thr Leu
325 330 335
Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys Tyr
340 345 350
Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val Ile
355 360 365
Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys Thr
370 375 380
Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly Cys
385 390 395 400
Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn Thr
405 410 415
Leu Tyr Cys Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys Gly
420 425 430
Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu
435 440 445
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
450 455 460
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
465 470
<210> 62
<211> 474
<212> PRT
<213> 人工序列
<220>
<223> sc9-10 DS-Cav1 A149C Y458C S46G K465Q S215P E92D
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (468)..(474)
<223> 可选地不存在
<400> 62
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Gly Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Asp Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Gly Ser Gly Ser Ala Ile Cys Ser Gly
100 105 110
Val Ala Val Cys Lys Val Leu His Leu Glu Gly Glu Val Asn Lys Ile
115 120 125
Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser Asn
130 135 140
Gly Val Ser Val Leu Thr Phe Lys Val Leu Asp Leu Lys Asn Tyr Ile
145 150 155 160
Asp Lys Gln Leu Leu Pro Ile Leu Asn Lys Gln Ser Cys Ser Ile Pro
165 170 175
Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu Leu
180 185 190
Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro Val
195 200 205
Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn Asp
210 215 220
Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val Gln
225 230 235 240
Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Cys Ile Ile Lys Glu Glu
245 250 255
Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp Thr
260 265 270
Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr Lys
275 280 285
Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr Cys
290 295 300
Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys Lys
305 310 315 320
Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Arg Thr Leu
325 330 335
Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys Tyr
340 345 350
Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val Ile
355 360 365
Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys Thr
370 375 380
Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly Cys
385 390 395 400
Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn Thr
405 410 415
Leu Tyr Cys Val Asn Lys Gln Glu Gly Gln Ser Leu Tyr Val Lys Gly
420 425 430
Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu
435 440 445
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
450 455 460
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
465 470
<210> 63
<211> 522
<212> PRT
<213> 人工序列
<220>
<223> SC-DM (N67I, S215P)
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (486)..(522)
<223> 可选地不存在
<400> 63
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Lys Ile Lys Cys Asn Gly Thr Asp Ala Lys Ile Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Gln Ala Arg Gly Ser Gly Ser
100 105 110
Gly Arg Ser Leu Gly Phe Leu Leu Gly Val Gly Ser Ala Ile Ala Ser
115 120 125
Gly Val Ala Val Ser Lys Val Leu His Leu Glu Gly Glu Val Asn Lys
130 135 140
Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser
145 150 155 160
Asn Gly Val Ser Val Leu Thr Ser Lys Val Leu Asp Leu Lys Asn Tyr
165 170 175
Ile Asp Lys Gln Leu Leu Pro Ile Val Asn Lys Gln Ser Cys Ser Ile
180 185 190
Pro Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu
195 200 205
Leu Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro
210 215 220
Val Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn
225 230 235 240
Asp Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val
245 250 255
Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Ser Ile Ile Lys Glu
260 265 270
Glu Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp
275 280 285
Thr Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr
290 295 300
Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr
305 310 315 320
Cys Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys
325 330 335
Lys Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Leu Thr
340 345 350
Leu Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys
355 360 365
Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val
370 375 380
Ile Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys
385 390 395 400
Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly
405 410 415
Cys Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn
420 425 430
Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys
435 440 445
Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp
450 455 460
Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
465 470 475 480
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Ser Ala Ile Gly Gly
485 490 495
Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp
500 505 510
Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
515 520
<210> 64
<211> 522
<212> PRT
<213> 人工序列
<220>
<223> SC-TM (N67I, S215P, and E487Q)
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (486)..(522)
<223> 可选地不存在
<400> 64
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Lys Ile Lys Cys Asn Gly Thr Asp Ala Lys Ile Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Gln Ala Arg Gly Ser Gly Ser
100 105 110
Gly Arg Ser Leu Gly Phe Leu Leu Gly Val Gly Ser Ala Ile Ala Ser
115 120 125
Gly Val Ala Val Ser Lys Val Leu His Leu Glu Gly Glu Val Asn Lys
130 135 140
Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser
145 150 155 160
Asn Gly Val Ser Val Leu Thr Ser Lys Val Leu Asp Leu Lys Asn Tyr
165 170 175
Ile Asp Lys Gln Leu Leu Pro Ile Val Asn Lys Gln Ser Cys Ser Ile
180 185 190
Pro Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu
195 200 205
Leu Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro
210 215 220
Val Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn
225 230 235 240
Asp Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val
245 250 255
Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Ser Ile Ile Lys Glu
260 265 270
Glu Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp
275 280 285
Thr Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr
290 295 300
Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr
305 310 315 320
Cys Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys
325 330 335
Lys Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Leu Thr
340 345 350
Leu Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys
355 360 365
Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val
370 375 380
Ile Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys
385 390 395 400
Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly
405 410 415
Cys Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn
420 425 430
Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys
435 440 445
Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp
450 455 460
Gln Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
465 470 475 480
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Ser Ala Ile Gly Gly
485 490 495
Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp
500 505 510
Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
515 520
<210> 65
<211> 490
<212> PRT
<213> 人工序列
<220>
<223> HMPV F蛋白，菌株CAN97-83（A2）
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 65
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Ala Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Thr
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Ile Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Ala Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly
485 490
<210> 66
<211> 490
<212> PRT
<213> 人工序列
<220>
<223> 具有A113C、A339C、T160F、I177L的HMPVF
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 66
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Cys Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Phe
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Leu Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Cys Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly
485 490
<210> 67
<211> 490
<212> PRT
<213> 人工序列
<220>
<223> 具有A113C、A120C、A339C、T160F、I177L和Q426C的HMPV-F
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 67
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Cys Thr Ala Ala Ala Val Thr Cys Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Phe
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Leu Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Cys Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Cys Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly
485 490
<210> 68
<211> 542
<212> PRT
<213> 人工序列
<220>
<223> 115-BV (A185P)
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (490)..(542)
<223> 可选地不存在
<400> 68
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ala Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Arg Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Arg Arg Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Ala Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Lys Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Thr
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Ile Asn Lys Asn Lys Cys Asp Ile Pro Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Glu Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Ala Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Val Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Ser Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Ser Gly Arg Glu Asn Leu Tyr
485 490 495
Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp
500 505 510
Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr
515 520 525
Phe Leu Gly Gly Ile Glu Gly Arg His His His His His His
530 535 540
<210> 69
<211> 646
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-折叠子-T33-31A
<220>
<221> 尚未归类的特征
<222> (1)..(26)
<223> 可选地不存在
<400> 69
Met Glu Leu Leu Ile Leu Lys Ala Asn Val Ile Ala Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg
515 520 525
Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Met
530 535 540
Glu Glu Val Val Leu Ile Thr Val Pro Ser Ala Leu Val Ala Val Lys
545 550 555 560
Ile Ala His Ala Leu Val Glu Glu Arg Leu Ala Ala Cys Val Asn Ile
565 570 575
Val Pro Gly Leu Thr Ser Ile Tyr Arg Glu Glu Gly Ser Val Val Ser
580 585 590
Asp His Glu Leu Leu Leu Leu Val Lys Thr Thr Thr Asp Ala Phe Pro
595 600 605
Lys Leu Lys Glu Arg Val Lys Glu Leu His Pro Tyr Glu Val Pro Glu
610 615 620
Ile Val Ala Leu Pro Ile Ala Glu Gly Asn Arg Glu Tyr Leu Asp Trp
625 630 635 640
Leu Arg Glu Asn Thr Gly
645
<210> 70
<211> 619
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-T33-31A
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 70
Met Glu Leu Leu Ile Leu Lys Ala Asn Val Ile Ala Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Gly Gly Ser Met Glu Glu Val Val Leu Ile Thr Val Pro Ser Ala
515 520 525
Leu Val Ala Val Lys Ile Ala His Ala Leu Val Glu Glu Arg Leu Ala
530 535 540
Ala Cys Val Asn Ile Val Pro Gly Leu Thr Ser Ile Tyr Arg Glu Glu
545 550 555 560
Gly Ser Val Val Ser Asp His Glu Leu Leu Leu Leu Val Lys Thr Thr
565 570 575
Thr Asp Ala Phe Pro Lys Leu Lys Glu Arg Val Lys Glu Leu His Pro
580 585 590
Tyr Glu Val Pro Glu Ile Val Ala Leu Pro Ile Ala Glu Gly Asn Arg
595 600 605
Glu Tyr Leu Asp Trp Leu Arg Glu Asn Thr Gly
610 615
<210> 71
<211> 665
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-折叠子-T33-15B
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 71
Met Glu Leu Leu Ile Leu Lys Ala Asn Val Ile Ala Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg
515 520 525
Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Met
530 535 540
Val Arg Gly Ile Arg Gly Ala Ile Thr Val Asn Ser Asp Thr Pro Thr
545 550 555 560
Ser Ile Ile Ile Ala Thr Ile Leu Leu Leu Glu Lys Met Leu Glu Ala
565 570 575
Asn Gly Ile Gln Ser Tyr Glu Glu Leu Ala Ala Val Ile Phe Thr Val
580 585 590
Thr Glu Asp Leu Thr Ser Ala Phe Pro Ala Glu Ala Ala Arg Gln Ile
595 600 605
Gly Met His Arg Val Pro Leu Leu Ser Ala Arg Glu Val Pro Val Pro
610 615 620
Gly Ser Leu Pro Arg Val Ile Arg Val Leu Ala Leu Trp Asn Thr Asp
625 630 635 640
Thr Pro Gln Asp Arg Val Arg His Val Tyr Leu Ser Glu Ala Val Arg
645 650 655
Leu Arg Pro Asp Leu Glu Ser Ala Gln
660 665
<210> 72
<211> 638
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-T33-15B
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 72
Met Glu Leu Leu Ile Leu Lys Ala Asn Val Ile Ala Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Gly Gly Ser Met Val Arg Gly Ile Arg Gly Ala Ile Thr Val Asn
515 520 525
Ser Asp Thr Pro Thr Ser Ile Ile Ile Ala Thr Ile Leu Leu Leu Glu
530 535 540
Lys Met Leu Glu Ala Asn Gly Ile Gln Ser Tyr Glu Glu Leu Ala Ala
545 550 555 560
Val Ile Phe Thr Val Thr Glu Asp Leu Thr Ser Ala Phe Pro Ala Glu
565 570 575
Ala Ala Arg Gln Ile Gly Met His Arg Val Pro Leu Leu Ser Ala Arg
580 585 590
Glu Val Pro Val Pro Gly Ser Leu Pro Arg Val Ile Arg Val Leu Ala
595 600 605
Leu Trp Asn Thr Asp Thr Pro Gln Asp Arg Val Arg His Val Tyr Leu
610 615 620
Ser Glu Ala Val Arg Leu Arg Pro Asp Leu Glu Ser Ala Gln
625 630 635
<210> 73
<211> 769
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-折叠子-I53-50A
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 73
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Tyr Ile Pro Glu
500 505 510
Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val
515 520 525
Leu Leu Ser Thr Phe Leu Gly Ser Gly Ser His His His His His His
530 535 540
His His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala
545 550 555 560
Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile
565 570 575
Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala
580 585 590
Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr
595 600 605
Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu
610 615 620
Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys
625 630 635 640
Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu
645 650 655
Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met
660 665 670
Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly
675 680 685
His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe
690 695 700
Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr
705 710 715 720
Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val
725 730 735
Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu
740 745 750
Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr
755 760 765
Glu
<210> 74
<211> 730
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-I53-50A
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 74
Met Glu Leu Leu Ile Leu Lys Ala Asn Val Ile Ala Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Gly Ser Gly Gly
500 505 510
Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met
515 520 525
Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn
530 535 540
Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly
545 550 555 560
Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val
565 570 575
Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala
580 585 590
Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly
595 600 605
Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe
610 615 620
Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr
625 630 635 640
Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe
645 650 655
Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro
660 665 670
Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn
675 680 685
Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser
690 695 700
Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala
705 710 715 720
Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
725 730
<210> 75
<211> 676
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-I32-28A
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 75
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Gly Gly Ser Gly Gly Ser Gly Ser Asp Asp Ala Arg Ile Ala Ala
515 520 525
Ile Gly Asp Val Asp Glu Leu Asn Ser Gln Ile Gly Val Leu Leu Ala
530 535 540
Glu Pro Leu Pro Asp Asp Val Arg Ala Ala Leu Ser Ala Ile Gln His
545 550 555 560
Asp Leu Phe Asp Leu Gly Gly Glu Leu Cys Ile Pro Gly His Ala Ala
565 570 575
Ile Thr Glu Asp His Leu Leu Arg Leu Ala Leu Trp Leu Val His Tyr
580 585 590
Asn Gly Gln Leu Pro Pro Leu Glu Glu Phe Ile Leu Pro Gly Gly Ala
595 600 605
Arg Gly Ala Ala Leu Ala His Val Cys Arg Thr Val Cys Arg Arg Ala
610 615 620
Glu Arg Ser Ile Lys Ala Leu Gly Ala Ser Glu Pro Leu Asn Ile Ala
625 630 635 640
Pro Ala Ala Tyr Val Asn Leu Leu Ser Asp Leu Leu Phe Val Leu Ala
645 650 655
Arg Val Leu Asn Arg Ala Ala Gly Gly Ala Asp Val Leu Trp Asp Arg
660 665 670
Thr Arg Ala His
675
<210> 76
<211> 730
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-8GS-HelExt-I53-50A (F10)
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 76
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Ser Gly Gly Ser
500 505 510
Gly Ser Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met
515 520 525
Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn
530 535 540
Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly
545 550 555 560
Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val
565 570 575
Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala
580 585 590
Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly
595 600 605
Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe
610 615 620
Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr
625 630 635 640
Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe
645 650 655
Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro
660 665 670
Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn
675 680 685
Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser
690 695 700
Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala
705 710 715 720
Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
725 730
<210> 77
<211> 764
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-折叠子-15GS-HelExt-I53-50A (F14)
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 77
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Tyr Ile Pro Glu
500 505 510
Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val
515 520 525
Leu Leu Ser Thr Phe Leu Gly Ser Gly Gly Ser Gly Ser Gly Ser Gly
530 535 540
Gly Ser Gly Ser Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg
545 550 555 560
Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg
565 570 575
Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala
580 585 590
Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp
595 600 605
Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile
610 615 620
Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu
625 630 635 640
Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser
645 650 655
Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr
660 665 670
Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys
675 680 685
Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys
690 695 700
Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu
705 710 715 720
Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val
725 730 735
Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala
740 745 750
Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
755 760
<210> 78
<211> 774
<212> PRT
<213> 人工序列
<220>
<223> HMPV F wt_CAN97-83菌剂-I53-50A
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 78
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Ala Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Thr
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Ile Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Ala Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Phe Ile Ile Val Ile Ile
485 490 495
Leu Ile Ala Val Leu Gly Ser Ser Met Ile Leu Val Ser Ile Phe Ile
500 505 510
Ile Ile Lys Lys Thr Lys Lys Pro Thr Gly Ala Pro Pro Glu Leu Ser
515 520 525
Gly Val Thr Asn Asn Gly Phe Ile Pro His Ser Gly Ser Gly Ser His
530 535 540
His His His His His His His Gly Gly Ser Gly Gly Ser Gly Ser Glu
545 550 555 560
Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe
565 570 575
Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu
580 585 590
Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile
595 600 605
Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu
610 615 620
Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr
625 630 635 640
Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile
645 650 655
Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys
660 665 670
Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys
675 680 685
Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val
690 695 700
Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val
705 710 715 720
Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp
725 730 735
Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys
740 745 750
Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys
755 760 765
Ile Arg Gly Cys Thr Glu
770
<210> 79
<211> 725
<212> PRT
<213> 人工序列
<220>
<223> HMPV F A113C_A339C_T160F_I177L-I53-50A
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 79
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Cys Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Phe
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Leu Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Cys Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Gly Ser Gly Ser His His
485 490 495
His His His His His His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys
500 505 510
Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys
515 520 525
Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala
530 535 540
Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu
545 550 555 560
Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser
565 570 575
Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser
580 585 590
Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val
595 600 605
Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly
610 615 620
Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala
625 630 635 640
Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val
645 650 655
Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys
660 665 670
Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe
675 680 685
Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly
690 695 700
Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile
705 710 715 720
Arg Gly Cys Thr Glu
725
<210> 80
<211> 725
<212> PRT
<213> 人工序列
<220>
<223> HMPV F A113C_A339C_T160F_I177L_A120C, Q426C - I53-50A
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 80
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Cys Thr Ala Ala Ala Val Thr Cys Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Phe
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Leu Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Cys Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Cys Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Gly Ser Gly Ser His His
485 490 495
His His His His His His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys
500 505 510
Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys
515 520 525
Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala
530 535 540
Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu
545 550 555 560
Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser
565 570 575
Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser
580 585 590
Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val
595 600 605
Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly
610 615 620
Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala
625 630 635 640
Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val
645 650 655
Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys
660 665 670
Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe
675 680 685
Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly
690 695 700
Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile
705 710 715 720
Arg Gly Cys Thr Glu
725
<210> 81
<211> 703
<212> PRT
<213> 人工序列
<220>
<223> sc-DS2-I53-50A
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 81
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Gly Ser Gly Ser Cys Ile Ala Ser Gly
100 105 110
Val Ala Val Cys Lys Val Leu His Leu Glu Gly Glu Val Asn Lys Ile
115 120 125
Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser Asn
130 135 140
Gly Val Ser Val Leu Thr Phe Lys Val Leu Asp Leu Lys Asn Tyr Ile
145 150 155 160
Asp Lys Gln Leu Leu Pro Ile Leu Asn Lys Gln Ser Cys Ser Ile Ser
165 170 175
Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu Leu
180 185 190
Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro Val
195 200 205
Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn Asp
210 215 220
Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val Gln
225 230 235 240
Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Cys Ile Ile Lys Glu Glu
245 250 255
Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp Thr
260 265 270
Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr Lys
275 280 285
Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr Cys
290 295 300
Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys Lys
305 310 315 320
Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Leu Thr Leu
325 330 335
Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys Tyr
340 345 350
Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val Ile
355 360 365
Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys Thr
370 375 380
Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly Cys
385 390 395 400
Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn Thr
405 410 415
Leu Tyr Cys Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys Gly
420 425 430
Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu
435 440 445
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
450 455 460
Ala Phe Ile Arg Gly Ser Gly Ser His His His His His His His His
465 470 475 480
Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu
485 490 495
Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala
500 505 510
Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala
515 520 525
Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro
530 535 540
Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly
545 550 555 560
Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys
565 570 575
Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu
580 585 590
Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly
595 600 605
Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr
610 615 620
Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys
625 630 635 640
Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly
645 650 655
Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala
660 665 670
Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg
675 680 685
Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
690 695 700
<210> 82
<211> 742
<212> PRT
<213> 人工序列
<220>
<223> tc-DS2-I53-50A
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 82
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Cys Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Cys Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Ser Gly Ser His
500 505 510
His His His His His His His Gly Gly Ser Gly Gly Ser Gly Ser Glu
515 520 525
Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe
530 535 540
Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu
545 550 555 560
Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile
565 570 575
Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu
580 585 590
Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr
595 600 605
Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile
610 615 620
Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys
625 630 635 640
Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys
645 650 655
Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val
660 665 670
Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val
675 680 685
Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp
690 695 700
Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys
705 710 715 720
Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys
725 730 735
Ile Arg Gly Cys Thr Glu
740
<210> 83
<211> 734
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-12GS-HelExt-I53-50A (F11)
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 83
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Ser Gly Gly Ser
500 505 510
Gly Ser Gly Ser Gly Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala
515 520 525
Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val
530 535 540
Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val
545 550 555 560
Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp
565 570 575
Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala
580 585 590
Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala
595 600 605
Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu
610 615 620
Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val
625 630 635 640
Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile
645 650 655
Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala
660 665 670
Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val
675 680 685
Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val
690 695 700
Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu
705 710 715 720
Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
725 730
<210> 84
<211> 738
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-16GS-HelExt-I53-50A (F12)
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 84
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Ser Gly Gly Ser
500 505 510
Gly Ser Gly Ser Gly Gly Ser Gly Ser Gly Gly Glu Lys Ala Ala Lys
515 520 525
Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys
530 535 540
Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys
545 550 555 560
Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe
565 570 575
Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys
580 585 590
Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln
595 600 605
Cys Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His
610 615 620
Leu Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr
625 630 635 640
Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu
645 650 655
Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln
660 665 670
Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro
675 680 685
Thr Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly
690 695 700
Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp
705 710 715 720
Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys
725 730 735
Thr Glu
<210> 85
<211> 759
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-折叠子-10GS-HelExt-I53-50A (F13)
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 85
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Tyr Ile Pro Glu
500 505 510
Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val
515 520 525
Leu Leu Ser Thr Phe Leu Gly Ser Gly Gly Ser Gly Ser Gly Ser Gly
530 535 540
Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu
545 550 555 560
Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu
565 570 575
Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu
580 585 590
Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala
595 600 605
Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val
610 615 620
Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala Glu Phe
625 630 635 640
Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu
645 650 655
Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val
660 665 670
Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu
675 680 685
Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn
690 695 700
Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Cys Glu
705 710 715 720
Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val
725 730 735
Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu
740 745 750
Lys Ile Arg Gly Cys Thr Glu
755
<210> 86
<211> 769
<212> PRT
<213> 人工序列
<220>
<223> DS-Cav1-折叠子-20GS-HelExt-I53-50A (F15)
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<400> 86
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Cys Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Phe Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Leu Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Cys Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Gly Tyr Ile Pro Glu
500 505 510
Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val
515 520 525
Leu Leu Ser Thr Phe Leu Gly Ser Gly Gly Ser Gly Ser Gly Ser Gly
530 535 540
Gly Ser Gly Ser Gly Gly Ser Ser Gly Ser Glu Lys Ala Ala Lys Ala
545 550 555 560
Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile
565 570 575
Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala
580 585 590
Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr
595 600 605
Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu
610 615 620
Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys
625 630 635 640
Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu
645 650 655
Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met
660 665 670
Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly
675 680 685
His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe
690 695 700
Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr
705 710 715 720
Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val
725 730 735
Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu
740 745 750
Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr
755 760 765
Glu
<210> 87
<211> 736
<212> PRT
<213> 人工序列
<220>
<223> sc9-10 DS-Cav1 A149C Y458C-折叠子-I53-50A实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (469)..(474)
<223> 可选地不存在
<400> 87
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Gly Ser Gly Ser Ala Ile Cys Ser Gly
100 105 110
Val Ala Val Cys Lys Val Leu His Leu Glu Gly Glu Val Asn Lys Ile
115 120 125
Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser Asn
130 135 140
Gly Val Ser Val Leu Thr Phe Lys Val Leu Asp Leu Lys Asn Tyr Ile
145 150 155 160
Asp Lys Gln Leu Leu Pro Ile Leu Asn Lys Gln Ser Cys Ser Ile Ser
165 170 175
Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu Leu
180 185 190
Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro Val
195 200 205
Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn Asp
210 215 220
Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val Gln
225 230 235 240
Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Cys Ile Ile Lys Glu Glu
245 250 255
Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp Thr
260 265 270
Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr Lys
275 280 285
Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr Cys
290 295 300
Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys Lys
305 310 315 320
Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Arg Thr Leu
325 330 335
Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys Tyr
340 345 350
Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val Ile
355 360 365
Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys Thr
370 375 380
Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly Cys
385 390 395 400
Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn Thr
405 410 415
Leu Tyr Cys Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys Gly
420 425 430
Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu
435 440 445
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
450 455 460
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Gly Tyr Ile Pro Glu Ala
465 470 475 480
Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu
485 490 495
Leu Ser Thr Phe Leu Gly Ser Gly Ser His His His His His His His
500 505 510
His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu
515 520 525
Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val
530 535 540
Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val
545 550 555 560
Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val
565 570 575
Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys
580 585 590
Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg
595 600 605
Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp
610 615 620
Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro
625 630 635 640
Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His
645 650 655
Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val
660 665 670
Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly
675 680 685
Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu
690 695 700
Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val
705 710 715 720
Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
725 730 735
<210> 88
<211> 697
<212> PRT
<213> 人工序列
<220>
<223> sc9-10 DS-Cav1 A149C Y458C - F10实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (469)..(474)
<223> 可选地不存在
<400> 88
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Gly Ser Gly Ser Ala Ile Cys Ser Gly
100 105 110
Val Ala Val Cys Lys Val Leu His Leu Glu Gly Glu Val Asn Lys Ile
115 120 125
Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser Asn
130 135 140
Gly Val Ser Val Leu Thr Phe Lys Val Leu Asp Leu Lys Asn Tyr Ile
145 150 155 160
Asp Lys Gln Leu Leu Pro Ile Leu Asn Lys Gln Ser Cys Ser Ile Ser
165 170 175
Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu Leu
180 185 190
Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro Val
195 200 205
Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn Asp
210 215 220
Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val Gln
225 230 235 240
Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Cys Ile Ile Lys Glu Glu
245 250 255
Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp Thr
260 265 270
Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr Lys
275 280 285
Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr Cys
290 295 300
Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys Lys
305 310 315 320
Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Arg Thr Leu
325 330 335
Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys Tyr
340 345 350
Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val Ile
355 360 365
Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys Thr
370 375 380
Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly Cys
385 390 395 400
Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn Thr
405 410 415
Leu Tyr Cys Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys Gly
420 425 430
Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu
435 440 445
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
450 455 460
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Gly Ser Gly Gly Ser Gly
465 470 475 480
Ser Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu
485 490 495
Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser
500 505 510
Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val
515 520 525
His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile
530 535 540
Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly
545 550 555 560
Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala
565 570 575
Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys
580 585 590
Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu
595 600 605
Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro
610 615 620
Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe
625 630 635 640
Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val
645 650 655
Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala
660 665 670
Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe
675 680 685
Val Glu Lys Ile Arg Gly Cys Thr Glu
690 695
<210> 89
<211> 736
<212> PRT
<213> 人工序列
<220>
<223> sc9-10 DS-Cav1 A149C Y458C S46G K465Q S215P E92D -折叠子-I53-50A
实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (469)..(474)
<223> 可选地不存在
<400> 89
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Gly Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Asp Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Gly Ser Gly Ser Ala Ile Cys Ser Gly
100 105 110
Val Ala Val Cys Lys Val Leu His Leu Glu Gly Glu Val Asn Lys Ile
115 120 125
Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser Asn
130 135 140
Gly Val Ser Val Leu Thr Phe Lys Val Leu Asp Leu Lys Asn Tyr Ile
145 150 155 160
Asp Lys Gln Leu Leu Pro Ile Leu Asn Lys Gln Ser Cys Ser Ile Pro
165 170 175
Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu Leu
180 185 190
Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro Val
195 200 205
Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn Asp
210 215 220
Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val Gln
225 230 235 240
Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Cys Ile Ile Lys Glu Glu
245 250 255
Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp Thr
260 265 270
Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr Lys
275 280 285
Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr Cys
290 295 300
Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys Lys
305 310 315 320
Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Arg Thr Leu
325 330 335
Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys Tyr
340 345 350
Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val Ile
355 360 365
Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys Thr
370 375 380
Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly Cys
385 390 395 400
Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn Thr
405 410 415
Leu Tyr Cys Val Asn Lys Gln Glu Gly Gln Ser Leu Tyr Val Lys Gly
420 425 430
Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu
435 440 445
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
450 455 460
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Gly Tyr Ile Pro Glu Ala
465 470 475 480
Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu
485 490 495
Leu Ser Thr Phe Leu Gly Ser Gly Ser His His His His His His His
500 505 510
His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu
515 520 525
Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val
530 535 540
Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val
545 550 555 560
Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val
565 570 575
Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys
580 585 590
Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg
595 600 605
Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp
610 615 620
Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro
625 630 635 640
Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His
645 650 655
Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val
660 665 670
Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly
675 680 685
Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu
690 695 700
Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val
705 710 715 720
Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
725 730 735
<210> 90
<211> 697
<212> PRT
<213> 人工序列
<220>
<223> sc9-10 DS-Cav1 A149C Y458C S46G K465Q S215P E92D - F10实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (469)..(474)
<223> 可选地不存在
<400> 90
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Gly Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Asp Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Gly Ser Gly Ser Ala Ile Cys Ser Gly
100 105 110
Val Ala Val Cys Lys Val Leu His Leu Glu Gly Glu Val Asn Lys Ile
115 120 125
Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser Asn
130 135 140
Gly Val Ser Val Leu Thr Phe Lys Val Leu Asp Leu Lys Asn Tyr Ile
145 150 155 160
Asp Lys Gln Leu Leu Pro Ile Leu Asn Lys Gln Ser Cys Ser Ile Pro
165 170 175
Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu Leu
180 185 190
Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro Val
195 200 205
Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn Asp
210 215 220
Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val Gln
225 230 235 240
Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Cys Ile Ile Lys Glu Glu
245 250 255
Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp Thr
260 265 270
Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr Lys
275 280 285
Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr Cys
290 295 300
Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys Lys
305 310 315 320
Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Arg Thr Leu
325 330 335
Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys Tyr
340 345 350
Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val Ile
355 360 365
Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys Thr
370 375 380
Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly Cys
385 390 395 400
Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn Thr
405 410 415
Leu Tyr Cys Val Asn Lys Gln Glu Gly Gln Ser Leu Tyr Val Lys Gly
420 425 430
Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu
435 440 445
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
450 455 460
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Gly Ser Gly Gly Ser Gly
465 470 475 480
Ser Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu
485 490 495
Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser
500 505 510
Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val
515 520 525
His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile
530 535 540
Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly
545 550 555 560
Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala
565 570 575
Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys
580 585 590
Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu
595 600 605
Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro
610 615 620
Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe
625 630 635 640
Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val
645 650 655
Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala
660 665 670
Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe
675 680 685
Val Glu Lys Ile Arg Gly Cys Thr Glu
690 695
<210> 91
<211> 753
<212> PRT
<213> 人工序列
<220>
<223> SC-DM (N67I, S215P) -折叠子-I53-50A实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (486)..(491)
<223> 可选地不存在
<400> 91
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Lys Ile Lys Cys Asn Gly Thr Asp Ala Lys Ile Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Gln Ala Arg Gly Ser Gly Ser
100 105 110
Gly Arg Ser Leu Gly Phe Leu Leu Gly Val Gly Ser Ala Ile Ala Ser
115 120 125
Gly Val Ala Val Ser Lys Val Leu His Leu Glu Gly Glu Val Asn Lys
130 135 140
Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser
145 150 155 160
Asn Gly Val Ser Val Leu Thr Ser Lys Val Leu Asp Leu Lys Asn Tyr
165 170 175
Ile Asp Lys Gln Leu Leu Pro Ile Val Asn Lys Gln Ser Cys Ser Ile
180 185 190
Pro Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu
195 200 205
Leu Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro
210 215 220
Val Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn
225 230 235 240
Asp Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val
245 250 255
Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Ser Ile Ile Lys Glu
260 265 270
Glu Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp
275 280 285
Thr Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr
290 295 300
Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr
305 310 315 320
Cys Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys
325 330 335
Lys Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Leu Thr
340 345 350
Leu Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys
355 360 365
Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val
370 375 380
Ile Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys
385 390 395 400
Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly
405 410 415
Cys Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn
420 425 430
Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys
435 440 445
Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp
450 455 460
Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
465 470 475 480
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Gly Tyr Ile Pro Glu
485 490 495
Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val
500 505 510
Leu Leu Ser Thr Phe Leu Gly Ser Gly Ser His His His His His His
515 520 525
His His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala
530 535 540
Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile
545 550 555 560
Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala
565 570 575
Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr
580 585 590
Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu
595 600 605
Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys
610 615 620
Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu
625 630 635 640
Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met
645 650 655
Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly
660 665 670
His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe
675 680 685
Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr
690 695 700
Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val
705 710 715 720
Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu
725 730 735
Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr
740 745 750
Glu
<210> 92
<211> 714
<212> PRT
<213> 人工序列
<220>
<223> SC-DM (N67I, S215P) - F10实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (486)..(491)
<223> 可选地不存在
<400> 92
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Lys Ile Lys Cys Asn Gly Thr Asp Ala Lys Ile Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Gln Ala Arg Gly Ser Gly Ser
100 105 110
Gly Arg Ser Leu Gly Phe Leu Leu Gly Val Gly Ser Ala Ile Ala Ser
115 120 125
Gly Val Ala Val Ser Lys Val Leu His Leu Glu Gly Glu Val Asn Lys
130 135 140
Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser
145 150 155 160
Asn Gly Val Ser Val Leu Thr Ser Lys Val Leu Asp Leu Lys Asn Tyr
165 170 175
Ile Asp Lys Gln Leu Leu Pro Ile Val Asn Lys Gln Ser Cys Ser Ile
180 185 190
Pro Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu
195 200 205
Leu Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro
210 215 220
Val Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn
225 230 235 240
Asp Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val
245 250 255
Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Ser Ile Ile Lys Glu
260 265 270
Glu Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp
275 280 285
Thr Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr
290 295 300
Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr
305 310 315 320
Cys Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys
325 330 335
Lys Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Leu Thr
340 345 350
Leu Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys
355 360 365
Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val
370 375 380
Ile Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys
385 390 395 400
Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly
405 410 415
Cys Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn
420 425 430
Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys
435 440 445
Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp
450 455 460
Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
465 470 475 480
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Gly Ser Gly Gly Ser
485 490 495
Gly Ser Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met
500 505 510
Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn
515 520 525
Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly
530 535 540
Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val
545 550 555 560
Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala
565 570 575
Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly
580 585 590
Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe
595 600 605
Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr
610 615 620
Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe
625 630 635 640
Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro
645 650 655
Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn
660 665 670
Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser
675 680 685
Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala
690 695 700
Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
705 710
<210> 93
<211> 753
<212> PRT
<213> 人工序列
<220>
<223> SC-TM (N67I、S215P和E487Q) - 折叠子-I53-50A实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (486)..(491)
<223> 可选地不存在
<400> 93
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Lys Ile Lys Cys Asn Gly Thr Asp Ala Lys Ile Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Gln Ala Arg Gly Ser Gly Ser
100 105 110
Gly Arg Ser Leu Gly Phe Leu Leu Gly Val Gly Ser Ala Ile Ala Ser
115 120 125
Gly Val Ala Val Ser Lys Val Leu His Leu Glu Gly Glu Val Asn Lys
130 135 140
Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser
145 150 155 160
Asn Gly Val Ser Val Leu Thr Ser Lys Val Leu Asp Leu Lys Asn Tyr
165 170 175
Ile Asp Lys Gln Leu Leu Pro Ile Val Asn Lys Gln Ser Cys Ser Ile
180 185 190
Pro Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu
195 200 205
Leu Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro
210 215 220
Val Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn
225 230 235 240
Asp Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val
245 250 255
Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Ser Ile Ile Lys Glu
260 265 270
Glu Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp
275 280 285
Thr Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr
290 295 300
Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr
305 310 315 320
Cys Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys
325 330 335
Lys Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Leu Thr
340 345 350
Leu Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys
355 360 365
Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val
370 375 380
Ile Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys
385 390 395 400
Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly
405 410 415
Cys Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn
420 425 430
Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys
435 440 445
Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp
450 455 460
Gln Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
465 470 475 480
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Gly Tyr Ile Pro Glu
485 490 495
Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val
500 505 510
Leu Leu Ser Thr Phe Leu Gly Ser Gly Ser His His His His His His
515 520 525
His His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala
530 535 540
Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile
545 550 555 560
Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala
565 570 575
Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr
580 585 590
Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu
595 600 605
Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys
610 615 620
Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu
625 630 635 640
Asp Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met
645 650 655
Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly
660 665 670
His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe
675 680 685
Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr
690 695 700
Gly Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val
705 710 715 720
Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu
725 730 735
Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr
740 745 750
Glu
<210> 94
<211> 714
<212> PRT
<213> 人工序列
<220>
<223> SC-TM (N67I、S215P和E487Q)-I53-50A - F10实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(25)
<223> 可选地不存在
<220>
<221> 尚未归类的特征
<222> (486)..(491)
<223> 可选地不存在
<400> 94
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Lys Ile Lys Cys Asn Gly Thr Asp Ala Lys Ile Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Gln Ala Arg Gly Ser Gly Ser
100 105 110
Gly Arg Ser Leu Gly Phe Leu Leu Gly Val Gly Ser Ala Ile Ala Ser
115 120 125
Gly Val Ala Val Ser Lys Val Leu His Leu Glu Gly Glu Val Asn Lys
130 135 140
Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser
145 150 155 160
Asn Gly Val Ser Val Leu Thr Ser Lys Val Leu Asp Leu Lys Asn Tyr
165 170 175
Ile Asp Lys Gln Leu Leu Pro Ile Val Asn Lys Gln Ser Cys Ser Ile
180 185 190
Pro Asn Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu
195 200 205
Leu Glu Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro
210 215 220
Val Ser Thr Tyr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn
225 230 235 240
Asp Met Pro Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val
245 250 255
Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile Met Ser Ile Ile Lys Glu
260 265 270
Glu Val Leu Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp
275 280 285
Thr Pro Cys Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr
290 295 300
Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr
305 310 315 320
Cys Asp Asn Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys
325 330 335
Lys Val Gln Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Leu Thr
340 345 350
Leu Pro Ser Glu Val Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys
355 360 365
Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val
370 375 380
Ile Thr Ser Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys
385 390 395 400
Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly
405 410 415
Cys Asp Tyr Val Ser Asn Lys Gly Val Asp Thr Val Ser Val Gly Asn
420 425 430
Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys
435 440 445
Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp
450 455 460
Gln Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
465 470 475 480
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu Gly Ser Gly Gly Ser
485 490 495
Gly Ser Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met
500 505 510
Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn
515 520 525
Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly
530 535 540
Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val
545 550 555 560
Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala
565 570 575
Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly
580 585 590
Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe
595 600 605
Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr
610 615 620
Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe
625 630 635 640
Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro
645 650 655
Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn
660 665 670
Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser
675 680 685
Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala
690 695 700
Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
705 710
<210> 95
<211> 752
<212> PRT
<213> 人工序列
<220>
<223> 具有A113C、A339C、T160F、I177L的HMPV-F-折叠子-I53-50A实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 95
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Cys Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Phe
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Leu Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Cys Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Gly Tyr Ile Pro Glu Ala
485 490 495
Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu
500 505 510
Leu Ser Thr Phe Leu Gly Ser Gly Ser His His His His His His His
515 520 525
His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu
530 535 540
Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val
545 550 555 560
Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val
565 570 575
Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val
580 585 590
Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys
595 600 605
Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg
610 615 620
Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp
625 630 635 640
Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro
645 650 655
Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His
660 665 670
Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val
675 680 685
Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly
690 695 700
Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu
705 710 715 720
Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val
725 730 735
Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
740 745 750
<210> 96
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> 具有A113C、A339C、T160F、I177L-I53-50A F10的HMPV-F实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 96
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Cys Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Phe
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Leu Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Cys Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Gly Ser Gly Gly Ser Gly
485 490 495
Ser Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu
500 505 510
Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser
515 520 525
Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val
530 535 540
His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile
545 550 555 560
Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly
565 570 575
Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala
580 585 590
Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys
595 600 605
Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu
610 615 620
Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro
625 630 635 640
Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe
645 650 655
Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val
660 665 670
Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala
675 680 685
Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe
690 695 700
Val Glu Lys Ile Arg Gly Cys Thr Glu
705 710
<210> 97
<211> 752
<212> PRT
<213> 人工序列
<220>
<223> 具有A113C、A120C、A339C、T160F、I177L和Q426C的HMPV-F-折叠子-I53-50A实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 97
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Cys Thr Ala Ala Ala Val Thr Cys Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Phe
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Leu Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Cys Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Cys Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Gly Tyr Ile Pro Glu Ala
485 490 495
Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu
500 505 510
Leu Ser Thr Phe Leu Gly Ser Gly Ser His His His His His His His
515 520 525
His Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu
530 535 540
Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val
545 550 555 560
Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val
565 570 575
Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val
580 585 590
Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys
595 600 605
Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg
610 615 620
Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp
625 630 635 640
Glu Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro
645 650 655
Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His
660 665 670
Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val
675 680 685
Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly
690 695 700
Gly Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu
705 710 715 720
Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val
725 730 735
Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
740 745 750
<210> 98
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> 具有A113C、A120C、A339C、T160F、I177L和Q426C的HMPV-F-F10实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 98
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ser Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Lys Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Cys Thr Ala Ala Ala Val Thr Cys Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Thr Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Phe
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Leu Asn Lys Asn Lys Cys Asp Ile Asp Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Cys Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Cys Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Ile Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Asn Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Gly Ser Gly Gly Ser Gly
485 490 495
Ser Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu
500 505 510
Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser
515 520 525
Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val
530 535 540
His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile
545 550 555 560
Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly
565 570 575
Thr Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala
580 585 590
Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys
595 600 605
Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu
610 615 620
Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro
625 630 635 640
Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe
645 650 655
Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val
660 665 670
Cys Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala
675 680 685
Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe
690 695 700
Val Glu Lys Ile Arg Gly Cys Thr Glu
705 710
<210> 99
<211> 751
<212> PRT
<213> 人工序列
<220>
<223> HMPV-F 115-BV（A185P）-折叠子-I53-50A实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 99
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ala Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Arg Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Arg Arg Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Ala Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Lys Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Thr
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Ile Asn Lys Asn Lys Cys Asp Ile Pro Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Glu Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Ala Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Val Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Ser Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Tyr Ile Pro Glu Ala Pro
485 490 495
Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu
500 505 510
Ser Thr Phe Leu Gly Ser Gly Ser His His His His His His His His
515 520 525
Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu
530 535 540
Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala
545 550 555 560
Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala
565 570 575
Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro
580 585 590
Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly
595 600 605
Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Cys Arg Lys
610 615 620
Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu
625 630 635 640
Glu Ile Ser Gln Phe Cys Lys Glu Lys Gly Val Phe Tyr Met Pro Gly
645 650 655
Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr
660 665 670
Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys
675 680 685
Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly
690 695 700
Val Asn Leu Asp Asn Val Cys Glu Trp Phe Lys Ala Gly Val Leu Ala
705 710 715 720
Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg
725 730 735
Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Cys Thr Glu
740 745 750
<210> 100
<211> 712
<212> PRT
<213> 人工序列
<220>
<223> HMPV-F 115-BV (A185P)-I53-50A - F10实施方案
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 100
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ala Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Arg Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Arg Arg Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Ala Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Lys Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Thr
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Ile Asn Lys Asn Lys Cys Asp Ile Pro Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Ile Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Glu Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Ala Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Val Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Ser Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly Ser Gly Gly Ser Gly Ser
485 490 495
Gly Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu
500 505 510
Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val
515 520 525
Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His
530 535 540
Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys
545 550 555 560
Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr
565 570 575
Val Thr Ser Val Glu Gln Cys Arg Lys Ala Val Glu Ser Gly Ala Glu
580 585 590
Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Cys Lys
595 600 605
Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu
610 615 620
Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly
625 630 635 640
Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro
645 650 655
Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Cys
660 665 670
Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu
675 680 685
Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val
690 695 700
Glu Lys Ile Arg Gly Cys Thr Glu
705 710
<210> 101
<211> 490
<212> PRT
<213> 人工序列
<220>
<223> HMPV F> AAK62968.2融合蛋白[人类偏肺炎病毒]
<220>
<221> 尚未归类的特征
<222> (1)..(18)
<223> 可选地不存在
<400> 101
Met Ser Trp Lys Val Val Ile Ile Phe Ser Leu Leu Ile Thr Pro Gln
1 5 10 15
His Gly Leu Lys Glu Ser Tyr Leu Glu Glu Ser Cys Ser Thr Ile Thr
20 25 30
Glu Gly Tyr Leu Ser Val Leu Arg Thr Gly Trp Tyr Thr Asn Val Phe
35 40 45
Thr Leu Glu Val Gly Asp Val Glu Asn Leu Thr Cys Ala Asp Gly Pro
50 55 60
Ser Leu Ile Lys Thr Glu Leu Asp Leu Thr Lys Ser Ala Leu Arg Glu
65 70 75 80
Leu Arg Thr Val Ser Ala Asp Gln Leu Ala Arg Glu Glu Gln Ile Glu
85 90 95
Asn Pro Arg Gln Ser Arg Phe Val Leu Gly Ala Ile Ala Leu Gly Val
100 105 110
Ala Thr Ala Ala Ala Val Thr Ala Gly Val Ala Ile Ala Lys Thr Ile
115 120 125
Arg Leu Glu Ser Glu Val Thr Ala Ile Lys Asn Ala Leu Lys Lys Thr
130 135 140
Asn Glu Ala Val Ser Thr Leu Gly Asn Gly Val Arg Val Leu Ala Thr
145 150 155 160
Ala Val Arg Glu Leu Lys Asp Phe Val Ser Lys Asn Leu Thr Arg Ala
165 170 175
Ile Asn Lys Asn Lys Cys Asp Ile Ala Asp Leu Lys Met Ala Val Ser
180 185 190
Phe Ser Gln Phe Asn Arg Arg Phe Leu Asn Val Val Arg Gln Phe Ser
195 200 205
Asp Asn Ala Gly Ile Thr Pro Ala Ile Ser Leu Asp Leu Met Thr Asp
210 215 220
Ala Glu Leu Ala Arg Ala Val Ser Asn Met Pro Thr Ser Ala Gly Gln
225 230 235 240
Ile Lys Leu Met Leu Glu Asn Arg Ala Met Val Arg Arg Lys Gly Phe
245 250 255
Gly Phe Leu Ile Gly Val Tyr Gly Ser Ser Val Ile Tyr Met Val Gln
260 265 270
Leu Pro Ile Phe Gly Val Ile Asp Thr Pro Cys Trp Ile Val Lys Ala
275 280 285
Ala Pro Ser Cys Ser Gly Lys Lys Gly Asn Tyr Ala Cys Leu Leu Arg
290 295 300
Glu Asp Gln Gly Trp Tyr Cys Gln Asn Ala Gly Ser Thr Val Tyr Tyr
305 310 315 320
Pro Asn Glu Lys Asp Cys Glu Thr Arg Gly Asp His Val Phe Cys Asp
325 330 335
Thr Ala Ala Gly Ile Asn Val Ala Glu Gln Ser Lys Glu Cys Asn Ile
340 345 350
Asn Ile Ser Thr Thr Asn Tyr Pro Cys Lys Val Ser Thr Gly Arg His
355 360 365
Pro Ile Ser Met Val Ala Leu Ser Pro Leu Gly Ala Leu Val Ala Cys
370 375 380
Tyr Lys Gly Val Ser Cys Ser Ile Gly Ser Asn Arg Val Gly Ile Ile
385 390 395 400
Lys Gln Leu Asn Lys Gly Cys Ser Tyr Ile Thr Asn Gln Asp Ala Asp
405 410 415
Thr Val Thr Ile Asp Asn Thr Val Tyr Gln Leu Ser Lys Val Glu Gly
420 425 430
Glu Gln His Val Ile Lys Gly Arg Pro Val Ser Ser Ser Phe Asp Pro
435 440 445
Val Lys Phe Pro Glu Asp Gln Phe Asn Val Ala Leu Asp Gln Val Phe
450 455 460
Glu Ser Ile Glu Asn Ser Gln Ala Leu Val Asp Gln Ser Asn Arg Ile
465 470 475 480
Leu Ser Ser Ala Glu Lys Gly Asn Thr Gly
485 490

Claims (43)

1.一种纳米结构，其包含：
(a)多个第一组件，每个第一组件包含多个相同的第一多肽；
(b)多个第二组件，每个第二组件包含多个相同的第二多肽，其中所述第二多肽不同于所述第一多肽；
其中，所述多个第一组件与所述多个第二组件非共价地相互作用以形成纳米结构；并且
其中，所述纳米结构在所述纳米结构的外部上显示一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段的多个拷贝。
2.根据权利要求1所述的纳米结构，其中：
(a)所述第一多肽包含沿其全长与选自由SEQ ID NO：1-51组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽；并且
(b)所述第二多肽包含沿其全长与选自由SEQ ID NO：1-51组成的组中的多肽的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
3.根据权利要求1或2所述的纳米结构，其中，所述一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段包含沿其全长与选自由SEQ ID NO：53、61-68和101组成的组中的多肽具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
4.根据权利要求1或2所述的纳米结构，其中，所述一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段包含沿其全长与选自由SEQ ID NO：53和61-64组成的组中的RSV F蛋白或其突变体具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，其中所述多肽包括以下残基中的一个或多个：67I、149C、458C、46G、465Q、215P、92D和487Q。
5.根据权利要求1或2所述的纳米结构，其中，所述一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段包含沿其全长与选自由SEQ ID NO：65-68和101组成的组中的MPV F蛋白或其突变体具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，其中所述多肽包括以下残基中的一个或多个：113C、120C、339C、160F、177L、185P和426C。
6.根据权利要求1-5中任一项所述的纳米结构，其中，所述第一多肽和所述第二多肽包含沿其全长与选自以下对的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽：
SEQ ID NO：1和SEQ ID NO：2(I53-34A和I53-34B)；
SEQ ID NO：3和SEQ ID NO：4(I53-40A和I53-40B)；
SEQ ID NO：3和SEQ ID NO：24(I53-40A和I53-40B.1)；
SEQ ID NO：23和SEQ ID NO：4(I53-40A.1和I53-40B)；
SEQ ID NO：35和SEQ ID NO：36(I53-40A属和I53-40B属)；
SEQ ID NO：5和SEQ ID NO：6(I53-47A和I53-47B)；
SEQ ID NO：5和SEQ ID NO：27(I53-47A和I53-47B.1)；
SEQ ID NO：5和SEQ ID NO：28(I53-47A和I53-47B.1NegT2)；
SEQ ID NO：25和SEQ ID NO：6(I53-47A.1和I53-47B)；
SEQ ID NO：25和SEQ ID NO：27(I53-47A.1和I53-47B.1)；
SEQ ID NO：25和SEQ ID NO：28(I53-47A.1和I53-47B.1NegT2)；
SEQ ID NO：26和SEQ ID NO：6(I53-47A.1NegT2和I53-47B)；
SEQ ID NO：26和SEQ ID NO：27(I53-47A.1NegT2和I53-47B.1)；
SEQ ID NO：26和SEQ ID NO：28(I53-47A.1NegT2和I53-47B.1NegT2)；
SEQ ID NO：37和SEQ ID NO：38(I53-47A属和I53-47B属)；
SEQ ID NO：7和SEQ ID NO：8(I53-50A和I53-50B)；
SEQ ID NO：7和SEQ ID NO：32(I53-50A和I53-50B.1)；
SEQ ID NO：7和SEQ ID NO：33(I53-50A和I53-50B.1NegT2)；
SEQ ID NO：7和SEQ ID NO：34(I53-50A和I53-50B.4PosT1)；
SEQ ID NO：29和SEQ ID NO：8(I53-50A.1和I53-50B)；
SEQ ID NO：29和SEQ ID NO：32(I53-50A.1和I53-50B.1)；
SEQ ID NO：29和SEQ ID NO：33(I53-50A.1和I53-50B.1NegT2)；
SEQ ID NO：29和SEQ ID NO：34(I53-50A.1和I53-50B.4PosT1)；
SEQ ID NO：30和SEQ ID NO：8(I53-50A.1NegT2和I53-50B)；
SEQ ID NO：30和SEQ ID NO：32(I53-50A.1NegT2和I53-50B.1)；
SEQ ID NO：30和SEQ ID NO：33(I53-50A.1NegT2和I53-50B.1NegT2)；
SEQ ID NO：30和SEQ ID NO：34(I53-50A.1NegT2和I53-50B.4PosT1)；
SEQ ID NO：31和SEQ ID NO：8(I53-50A.1PosT1和I53-50B)；
SEQ ID NO：31和SEQ ID NO：32(I53-50A.1PosT1和I53-50B.1)；
SEQ ID NO：31和SEQ ID NO：33(I53-50A.1PosT1和I53-50B.1NegT2)；
SEQ ID NO：31和SEQ ID NO：34(I53-50A.1PosT1和I53-50B.4PosT1)；
SEQ ID NO：39和SEQ ID NO：40(I53-50A属和I53-50B属)；
SEQ ID NO：9和SEQ ID NO：10(I53-51A和I53-51B)；
SEQ ID NO：11和SEQ ID NO：12(I52-03A和I52-03B)；
SEQ ID NO：13和SEQ ID NO：14(I52-32A和I52-32B)；
SEQ ID NO：15和SEQ ID NO：16(I52-33A和I52-33B)
SEQ ID NO：17和SEQ ID NO：18(I32-06A和I32-06B)；
SEQ ID NO：19和SEQ ID NO：20(I32-19A和I32-19B)；
SEQ ID NO：21和SEQ ID NO：22(I32-28A和I32-28B)；
SEQ ID NO：23和SEQ ID NO：24(I53-40A.1和I53-40B.1)；
SEQ ID NO：41和SEQ ID NO：42(T32-28A和T32-28B)；
SEQ ID NO：43和SEQ ID NO：44(T33-09A和T33-09B)；
SEQ ID NO：45和SEQ ID NO：46(T33-15A和T33-15B)；
SEQ ID NO：47和SEQ ID NO：48(T33-21A和T33-21B)；
SEQ ID NO：49和SEQ ID NO：50(T33-28A和T32-28B)；和
SEQ ID NO：51和SEQ ID NO：44(T33-31B和T33-09B(也称为T33-31B))。
7.根据权利要求1-6中任一项所述的纳米结构，其中，所述第一多肽包含沿其全长与氨基酸序列T33-31A(SEQ ID NO：51)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列T33-09B/T33-31B(SEQ ID NO：44)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
8.根据权利要求1-6中任一项所述的纳米结构，其中，所述第一多肽包含沿其全长与氨基酸序列T33-15B(SEQ ID NO：46)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列T33-15A(SEQ ID NO：45)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
9.根据权利要求1-6中任一项所述的纳米结构，其中，所述第一多肽包含沿其全长与选自由I53-50A(SEQ ID NO：7)、I53-50A.1(SEQ ID NO：29)、I53-50A.1NegT2(SEQ ID NO：30)和I53-50A.1PosT1(SEQ ID NO：31)组成的组中的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与选自由I53-50B(SEQ ID NO：8)、I53-50B.1(SEQ ID NO：32)、I53-50B.1NegT2(SEQ ID NO：33)和I53-50B.4PosT1(SEQ ID NO：34)组成的组中的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
10.根据权利要求1-6中任一项所述的纳米结构，其中，所述第一多肽包含沿其全长与氨基酸序列I32-28A(SEQ ID NO：21)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽，并且所述第二多肽包含沿其全长与氨基酸序列I32-28B(SEQ ID NO：22)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
11.根据权利要求1-10中任一项所述的纳米结构，其中，将所述一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段表达为与所述第一多肽的融合蛋白。
12.根据权利要求11所述的纳米结构，其中，所述多个第一组件各自包含相同的融合蛋白。
13.根据权利要求11所述的纳米结构，其中，所述多个第一组件总共包括两个或多个副粘病毒和/或肺炎病毒F蛋白或其抗原片段。
14.根据权利要求11或12所述的纳米结构，其中，仅所述第一多肽的子集包含具有F蛋白或其抗原片段的融合蛋白。
15.根据权利要求1-14中任一项所述的纳米结构，其中，每个第一组件包含所述第一多肽的同源三聚体。
16.根据权利要求1-15中任一项所述的纳米结构，其中，所述一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段包含沿其全长与氨基酸序列DS-Cav1(SEQ ID NO：53)具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
17.根据权利要求11-16中任一项所述的纳米结构，其中，所述融合蛋白包含位于所述第一多肽与所述一种或多种副粘病毒和/或肺炎病毒F蛋白或其抗原片段之间的氨基酸接头。
18.根据权利要求17所述的纳米结构，其中，所述氨基酸接头序列包含一个或多个三聚化结构域。
19.根据权利要求17或18所述的纳米结构，其中，所述氨基酸接头序列包括氨基酸序列GYIPEAPRDGQAYVRKDGEWVLLSTFL(SEQ ID NO：54)。
20.根据权利要求17所述的纳米结构，其中，所述氨基酸接头序列包含Gly-Ser接头。
21.根据权利要求11-20中任一项所述的纳米结构，其中，所述融合蛋白包含沿其全长与选自由SEQ ID NO：69-100组成的组中的氨基酸序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的多肽。
22.根据权利要求21所述的纳米结构，其中：
(a)当每个融合蛋白是DS-Cav1-折叠子-T33-31A(SEQ ID NO：69)或DS-Cav1-T33-31A(SEQ ID NO：70)时，每个第二多肽是T33-31B(SEQ ID NO：70)NO：44)；
(b)当每个融合蛋白是DS-Cav1-折叠子-T33-15B(SEQ ID NO：71)或DS-Cav1-T33-15B(SEQ ID NO：72)时，每个第二多肽是T33-15A(SEQ ID NO：45)；
(c)当每个融合蛋白是DS-Cav1-折叠子-I53-50A(SEQ ID NO：73)或DS-Cav1-I53-50A(SEQ ID NO：74)时，每个第二多肽是I53-50B(SEQ ID NO：8)、I53-50B.1(SEQ ID NO：32)、I53-50B.1NegT2(SEQ ID NO：33)或I53-50B.4PosT1(SEQ ID NO：34)；或者
(d)当每个融合蛋白是DS-Cav1-I32-28A(SEQ ID NO：75)时，每个第二多肽是I32-28B(SEQ ID NO：22)。
23.根据权利要求16所述的纳米结构，其中，每个第一多肽包含通过氨基酸接头与SEQID NO：7(I53-50A)连接的DS-Cav1(SEQ ID NO：53)的融合蛋白。
24.根据权利要求23所述的纳米结构，其中，所述氨基酸接头序列包含Gly-Ser接头和/或螺旋延伸结构域。
25.根据权利要求11-24中任一项所述的纳米结构，其中，每个融合蛋白包含选自由SEQID NO：69-77和81-90组成的组中的氨基酸序列。
26.根据权利要求23-24中任一项所述的纳米结构，其中，每个融合蛋白包含氨基酸序列SEQ ID NO：76(F10)。
27.根据权利要求23-25中任一项所述的纳米结构，其中，每个第二多肽包含选自由I53-50B(SEQ ID NO：8)、I53-50B.1(SEQ ID NO：32)、I53-50B.1NegT2(SEQ ID NO：33)或I53-50B.4PosT1(SEQ ID NO：34)组成的组中的氨基酸序列。
28.根据权利要求23-27中任一项所述的纳米结构，其中，每个第二多肽包含氨基酸序列I53-50B.4PosT1(SEQ ID NO：34)。
29.根据权利要求1-28中任一项所述的纳米结构，其中，所述纳米结构：
(a)结合融合前F特异性抗体，包括但不限于单克隆抗体25；
(b)形成对称结构，包括但不限于二十面体结构；
(c)在50℃下是稳定的；和/或
(d)在2.25M盐酸胍中是稳定的。
30.一种重组核酸，其编码根据权利要求11-29中任一项所述的第一多肽融合蛋白。
31.一种重组表达载体，其包含与启动子可操作地连接的根据权利要求30所述的重组核酸。
32.一种重组宿主细胞，其包含根据权利要求31所述的重组表达载体。
33.一种重组宿主细胞，其包含一个或多个能够表达根据权利要求1-29中任一项所述的第一多肽和第二多肽的重组表达载体。
34.一种免疫原性组合物，其包含根据权利要求1-29中任一项所述的纳米结构和药学上可接受的载体。
35.根据权利要求34所述的免疫原性组合物，其进一步包含佐剂。
36.一种用于在受试者中对副粘病毒和/或肺炎病毒F蛋白产生免疫应答的方法，其包括向有此需要的受试者施用有效量的根据权利要求1-29和34-35中任一项所述的纳米结构或免疫原性组合物以产生所述免疫应答。
37.一种用于治疗或限制受试者的副粘病毒和/或肺炎病毒感染的方法，其包括向有此需要的受试者施用有效量的根据权利要求1-29和34-35中任一项所述的纳米结构或免疫原性组合物，从而治疗或预防所述受试者的副粘病毒和/或肺炎病毒感染。
38.根据权利要求36或37所述的方法，其中，所述施用导致在所述受试者中产生副粘病毒和/或肺炎病毒中和抗体。
39.根据权利要求39所述的方法，其中，所述中和抗体以至少9400的滴度(1/ID50)存在于所述受试者的血清中。
40.一种在体外组装根据权利要求1-29中任一项所述的纳米结构的工艺，其包括在水性条件下将两种或更多种纳米结构组分混合以驱动所需纳米结构的自发组装。
41.根据权利要求40所述的工艺，其中，所述混合包括在适于允许第一组件和第二组件相互作用以形成纳米结构的条件和时间下将包含各自含有F蛋白或其抗原片段(“F蛋白”)的第一多肽(例如三聚体第一多肽)的第一组件与包含第二多肽的适当第二组件以第一多肽：第二多肽的约1：1摩尔比混合。
42.根据权利要求40所述的工艺，其中，所述混合包括在适于允许第一组件和第二组件相互作用以形成纳米结构的条件和时间下将包含第一多肽(例如三聚体第一多肽)的第一组件与包含第二多肽的适当第二组件以第一多肽：第二多肽的约1：1摩尔比混合，其中少于所有第一多肽(例如75％、50％、25％等)包含F蛋白。
43.根据权利要求40所述的工艺，其中，所述混合包括在适于允许第一组件和第二组件相互作用以形成包含多个F蛋白或其抗原片段的纳米结构的条件和时间下将包含各自含有F蛋白的第一多肽(例如三聚体第一多肽)的第一组件与包含第二多肽的适当第二组件以第一多肽：第二多肽的约1：1摩尔比混合，其中所述第一多肽总共包含多个不同的F蛋白(例如2、3、4个或更多个)。
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