• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

理解 B 组链球菌保护性菌毛 2a 骨干蛋白免疫特异性的分子决定因素。

Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.

机构信息

Novartis Vaccines and Diagnostics, Siena, Italy.

出版信息

PLoS Comput Biol. 2013;9(6):e1003115. doi: 10.1371/journal.pcbi.1003115. Epub 2013 Jun 27.

DOI:10.1371/journal.pcbi.1003115
PMID:23825940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3694817/
Abstract

The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To investigate the molecular determinants driving the variant immunogenic specificity of BP-2a, in terms of single residue contributions, we generated six monoclonal antibodies against a specific protein variant based on their capability to recognize the polymerized pili structure on the bacterial surface. Three mAbs were also able to induce complement-dependent opsonophagocytosis killing of live GBS and target the same linear epitope present in the structurally defined and immunodominant domain D3 of the protein. Molecular docking between the modelled scFv antibody sequences and the BP-2a crystal structure revealed the potential role at the binding interface of some non-conserved antigen residues. Mutagenesis analysis confirmed the necessity of a perfect balance between charges, size and polarity at the binding interface to obtain specific binding of mAbs to the protein antigen for a neutralizing response.

摘要

纤毛 2a 骨干蛋白（BP-2a）是针对 B 群链球菌潜在疫苗制剂中结构和功能最具特征性的成分之一。它的特点是有六个主要的免疫上不同的等位基因变异体，每个变异体都能诱导特定的保护性免疫。为了研究 BP-2a 变体免疫原性特异性的分子决定因素，就单残基贡献而言，我们根据其识别细菌表面聚合菌毛结构的能力，针对特定蛋白变体生成了六种单克隆抗体。其中三种 mAb 还能够诱导补体依赖性调理吞噬作用杀死活的 GBS，并靶向该蛋白结构定义和免疫显性结构域 D3 中存在的相同线性表位。建模的 scFv 抗体序列与 BP-2a 晶体结构之间的分子对接揭示了在结合界面上一些非保守抗原残基的潜在作用。突变分析证实，在结合界面上获得 mAb 对蛋白质抗原的特异性结合以产生中和反应时，电荷、大小和极性之间需要达到完美平衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/d4d097caae46/pcbi.1003115.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/800b1cada722/pcbi.1003115.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/377e44eb3a28/pcbi.1003115.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/49d9c459286d/pcbi.1003115.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/039a5d0c788f/pcbi.1003115.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/cc02b1fccbb2/pcbi.1003115.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/c7be117b54b8/pcbi.1003115.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/d4d097caae46/pcbi.1003115.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/800b1cada722/pcbi.1003115.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/377e44eb3a28/pcbi.1003115.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/49d9c459286d/pcbi.1003115.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/039a5d0c788f/pcbi.1003115.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/cc02b1fccbb2/pcbi.1003115.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/c7be117b54b8/pcbi.1003115.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/3694817/d4d097caae46/pcbi.1003115.g007.jpg

相似文献

1
Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.理解 B 组链球菌保护性菌毛 2a 骨干蛋白免疫特异性的分子决定因素。
PLoS Comput Biol. 2013;9(6):e1003115. doi: 10.1371/journal.pcbi.1003115. Epub 2013 Jun 27.
2
Structure and assembly of group B streptococcus pilus 2b backbone protein.B族链球菌菌毛2b主链蛋白的结构与组装
PLoS One. 2015 May 5;10(5):e0125875. doi: 10.1371/journal.pone.0125875. eCollection 2015.
3
Sortase A substrate specificity in GBS pilus 2a cell wall anchoring.GBS 菌毛 2a 细胞壁锚定中 Sortase A 底物特异性。
PLoS One. 2011;6(10):e25300. doi: 10.1371/journal.pone.0025300. Epub 2011 Oct 4.
4
In silico analysis of candidate proteins sharing homology with Streptococcus agalactiae proteins and their role in male infertility.与无乳链球菌蛋白具有同源性的候选蛋白的计算机分析及其在男性不育中的作用。
Syst Biol Reprod Med. 2017 Feb;63(1):15-28. doi: 10.1080/19396368.2016.1243741. Epub 2016 Nov 1.
5
Genetic evidence for a novel variant of the pilus island 1 backbone protein in group B Streptococcus.B族链球菌菌毛岛1主链蛋白新变体的遗传学证据。
J Med Microbiol. 2017 Oct;66(10):1409-1415. doi: 10.1099/jmm.0.000588. Epub 2017 Sep 19.
6
Evidence for the Sialylation of PilA, the PI-2a Pilus-Associated Adhesin of Streptococcus agalactiae Strain NEM316.无乳链球菌NEM316菌株PI-2a菌毛相关黏附素PilA的唾液酸化证据
PLoS One. 2015 Sep 25;10(9):e0138103. doi: 10.1371/journal.pone.0138103. eCollection 2015.
7
Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections.基于结构的方法设计嵌合蛋白作为预防 B 族链球菌感染的有效疫苗
Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10278-83. doi: 10.1073/pnas.1106590108. Epub 2011 May 18.
8
New broadly reactive neutralizing antibodies against hepatitis B virus surface antigen.新型针对乙肝病毒表面抗原的广泛反应性中和抗体。
Virus Res. 2016 Jan 4;211:209-21. doi: 10.1016/j.virusres.2015.10.024. Epub 2015 Nov 2.
9
Structure analysis and site-directed mutagenesis of defined key residues and motives for pilus-related sortase C1 in group B Streptococcus.B 群链球菌菌毛相关的 sortase C1 中特定关键残基和基序的结构分析和定点突变。
FASEB J. 2011 Jun;25(6):1874-86. doi: 10.1096/fj.10-174797. Epub 2011 Feb 25.
10
Identification of an immunoglobulin A binding motif located in the beta-antigen of the c protein complex of group B streptococci.B族链球菌c蛋白复合物β抗原中免疫球蛋白A结合基序的鉴定。
Infect Immun. 1996 Jul;64(7):2787-93. doi: 10.1128/iai.64.7.2787-2793.1996.

引用本文的文献

1
Peptides for Infectious Diseases: From Probe Design to Diagnostic Microarrays.用于传染病的肽：从探针设计到诊断微阵列
Antibodies (Basel). 2019 Mar 12;8(1):23. doi: 10.3390/antib8010023.
2
A Secondary Antibody-Detecting Molecular Weight Marker with Mouse and Rabbit IgG Fc Linear Epitopes for Western Blot Analysis.一种用于蛋白质印迹分析的具有小鼠和兔IgG Fc线性表位的二抗检测分子量标记物。
PLoS One. 2016 Aug 5;11(8):e0160418. doi: 10.1371/journal.pone.0160418. eCollection 2016.
3
Structural conservation, variability, and immunogenicity of the T6 backbone pilin of serotype M6 Streptococcus pyogenes.

本文引用的文献

1
Sortase A substrate specificity in GBS pilus 2a cell wall anchoring.GBS 菌毛 2a 细胞壁锚定中 Sortase A 底物特异性。
PLoS One. 2011;6(10):e25300. doi: 10.1371/journal.pone.0025300. Epub 2011 Oct 4.
2
Molecular basis of antigenic drift in Influenza A/H3N2 strains (1968-2007) in the light of antigenantibody interactions.基于抗原-抗体相互作用视角的甲型H3N2流感病毒株（1968 - 2007年）抗原漂移的分子基础
Bioinformation. 2011;6(7):266-70. doi: 10.6026/97320630006266. Epub 2011 Jun 23.
3
Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections.
M6 型化脓性链球菌 T6 骨干菌毛的结构保守性、变异性和免疫原性。
Infect Immun. 2014 Jul;82(7):2949-57. doi: 10.1128/IAI.01706-14. Epub 2014 Apr 28.
基于结构的方法设计嵌合蛋白作为预防 B 族链球菌感染的有效疫苗
Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10278-83. doi: 10.1073/pnas.1106590108. Epub 2011 May 18.
4
MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.MEGA5：用于最大似然法、进化距离法和最大简约法的分子进化遗传学分析。
Mol Biol Evol. 2011 Oct;28(10):2731-9. doi: 10.1093/molbev/msr121. Epub 2011 May 4.
5
Structural and biochemical characterization of NarE, an iron-containing ADP-ribosyltransferase from Neisseria meningitidis.脑膜炎奈瑟菌中含有铁的 ADP-ribosyltransferase NarE 的结构和生化特性研究。
J Biol Chem. 2011 Apr 29;286(17):14842-51. doi: 10.1074/jbc.M110.193623. Epub 2011 Mar 2.
6
Elicitation of structure-specific antibodies by epitope scaffolds.表位支架诱导结构特异性抗体。
Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17880-7. doi: 10.1073/pnas.1004728107. Epub 2010 Sep 27.
7
Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope.基于表位支架的计算设计可诱导针对 HIV 疫苗弱免疫原性表位的特异性抗体。
Structure. 2010 Sep 8;18(9):1116-26. doi: 10.1016/j.str.2010.06.010.
8
Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology.Datamonkey 2010：一套用于进化生物学的系统发育分析工具。
Bioinformatics. 2010 Oct 1;26(19):2455-7. doi: 10.1093/bioinformatics/btq429. Epub 2010 Jul 29.
9
Exploiting antigenic diversity for vaccine design: the chlamydia ArtJ paradigm.利用抗原多样性进行疫苗设计：衣原体 ArtJ 范例。
J Biol Chem. 2010 Sep 24;285(39):30126-38. doi: 10.1074/jbc.M110.118513. Epub 2010 Jun 30.
10
Improved side-chain torsion potentials for the Amber ff99SB protein force field.改进的 Amber ff99SB 蛋白质力场的侧链扭转势。
Proteins. 2010 Jun;78(8):1950-8. doi: 10.1002/prot.22711.