Conformational flexibility in a highly mobile protein loop of foot-and-mouth disease virus:: Distinct structural requirements for integrin and antibody binding
Conformational flexibility in a highly mobile protein loop of foot-and-mouth disease virus:: Distinct structural requirements for integrin and antibody binding
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DOI：
10.1006/jmbi.1998.2104
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发表时间：
1998-10-23
影响因子：
5.6
通讯作者：
Villaverde, A
中科院分区：
文献类型：
--
作者：
Feliu, JX;Benito, A;Villaverde, A
口蹄疫病毒VP 1蛋白的G-H环是一个高度移动的肽段，它从衣壳表面延伸，在天然病毒体中通过X-Pay晶体学是不可见的。在血清型C中，该片段包含一个高变区，该高变区具有几个连续的、重叠的B细胞表位，这些表位包含保守的Arg-Gly-Asp（RGD）细胞附着基序。通过选择性插入到E.大肠杆菌β-半乳糖苷酶产生一系列抗原变体，这些变体与一组抗VP 1单克隆抗体特异性反应，并表现出作为细胞配体的不同效率。细胞附着效率受病毒片段在插入位点的不同定位的限制要小得多。一个插入的伸展的分子模型揭示了最高的灵活性的RGD三肽段相比，侧翼序列，可以允许一个适当的住宿整合素受体，即使在抗原性差的构象。RGD介导的整联蛋白结合和抗体识别的非收敛结构要求解释了病毒准种中产生中和抗性抗原变体的动力学，其产生于整联蛋白结合活性肽的构象空间。这可能与口蹄疫病毒的进化特别相关，因为与其他小核糖核酸病毒不同，在缺乏峡谷和类似隐藏结构的病毒体中，细胞结合基序和主要中和B细胞表位在宿主免疫系统可接近的溶剂暴露肽中重叠。(C)北京：科学出版社.
The G-H loop of foot-and-mouth disease virus VP1 protein is a highly mobile peptide, that extends from the capsid surface and that in native virions is invisible by X-Pay crystallography, In serotype C, this segment contains a hypervariable region with several continuous, overlapping, B-cell epitopes that embrace the conserved Arg-Gly-Asp (RGD) cell attachment motif. The solvent-exposed positioning of this peptide by selective insertion into different structural frameworks of E. coli beta-galactosidase, generates a spectrum of antigenic variants which react distinctively with a panel of anti-VP1 monoclonal antibodies and exhibit different efficiencies as cell ligands. The cell attachment efficiency is much less restricted by the different positioning of the viral segment at the insertion sites. A molecular model of an inserted stretch reveals a highest flexibility of the RGD tripeptide segment compared with the flanking sequences, that could allow a proper accommodation to integrin receptors even in poorly antigenic conformations. The non-converging structural requirements for RGD-mediated integrin binding and antibody recognition, explains the dynamism of the generation of neutralisation-resistant antigenic variants in the viral quasi-species, arising from a conformational space of integrin-binding competent peptides. This might be of special relevance for foot-and-moth disease virus evolution, since unlike in other picornaviruses, the cell binding motif and the major neutralising B-cell epitopes overlap in a solvent-exposed peptide accessible to the host immune system, in a virion lacking canyons and similar hiding structures. (C) 1998 Academic Press.