Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization.
Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization.
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DOI：
10.1016/j.virol.2015.04.016
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发表时间：
2015-09
期刊：
影响因子：
3.7
通讯作者：
Hafenstein S
中科院分区：
文献类型：
--
作者：
Guan J;Bywaters SM;Brendle SA;Lee H;Ashley RE;Makhov AM;Conway JF;Christensen ND;Hafenstein S
使用冷冻电子显微镜 (cryo-EM) 解析与来自三种不同中和单克隆抗体 (mAb) 的抗体 (Fab) 片段复合的人乳头瘤病毒 16 型 (HPV16) 的结构：H16.1A、H16.14J 和 H263.A2。结构-功能分析揭示了每个 Fab 与衣壳相互作用的主要单价结合，涉及主要衣壳蛋白的对称相关拷贝的多个环。每个 Fab 病毒界面中识别的残基映射到衣壳表面的构象凹槽。除了已知的 FG 和 HI 环参与外，还发现 DE 环构成每个表位的核心。令人惊讶的是，表位作图还发现了 EF 和 BC 环的次要贡献。补充免疫学测定包括 mAb 和 Fab 中和。 mAb 的特异性结合特性与附着前和附着后中和测定中的不同中和行为相关。
Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding of each Fab with capsid interactions that involved multiple loops from symmetry related copies of the major capsid protein. The residues identified in each Fab-virus interface map to a conformational groove on the surface of the capsomer. In addition to the known involvement of the FG and HI loops, the DE loop was also found to constitute the core of each epitope. Surprisingly, the epitope mapping also identified minor contributions by EF and BC loops. Complementary immunological assays included mAb and Fab neutralization. The specific binding characteristics of mAbs correlated with different neutralizing behaviors in pre- and post-attachment neutralization assays.