Open AccessA conserved epitope III on hepatitis C virus E2 protein has alternate conformations facilitating cell binding or virus neutralization
Author(s) -
Lu Deng,
Nancy Hernandez,
Li Zhong,
David D. Holcomb,
Hailing Yan,
M. L.A. Virata,
Sreya Tarafdar,
Yanqun Xu,
Yong He,
Evi Struble,
Harvey J. Alter,
Pei Zhang
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2104242118
Subject(s) - epitope , linear epitope , monoclonal antibody , mimotope , protein structure , cd81 , chemistry , virology , complementarity determining region , antibody , binding site , conformational epitope , epitope mapping , biology , peptide sequence , virus , biochemistry , hepatitis c virus , genetics , gene
Significance Epitope III, a segment on the E2 glycoprotein of the hepatitis C virus (HCV) which binds to the host receptor CD81, is a key target for antibodies to block HCV entry. By solving the atomic structure of epitope III bound to a site-specific neutralizing antibody, mAb1H8, we showed that the epitope can adopt two distinct conformations by moving the side chains of its amino acids, allowing it to bind with either mAb1H8 or CD81. The coexistence of different conformational states of epitope III suggests its possible role in the regulation of antibody responses. These findings should help to design strategies to control HCV infection by tipping the balance toward epitope III conformations that favor antibody recognition rather than CD81 binding.