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• W3181245184 startingPage "e2104242118" @default.
• W3181245184 abstract "Epitope III, a highly conserved amino acid motif of 524APTYSW529 on the hepatitis C virus (HCV) E2 glycoprotein, resides in the critical loop that binds to the host receptor CD81, thus making it one of the most important antibody targets for blocking HCV infections. Here, we have determined the X-ray crystal structure of epitope III at a 2.0-Å resolution when it was captured by a site-specific neutralizing antibody, monoclonal antibody 1H8 (mAb1H8). The snapshot of this complex revealed that epitope III has a relatively rigid structure when confined in the binding grooves of mAb1H8, which confers the residue specificity at both ends of the epitope. Such a high shape complementarity is reminiscent of the lock and key mode of action, which is reinforced by the incompatibility of an antibody binding with an epitope bearing specific mutations. By subtly positioning the side chains on the three residues of Tyr527, Ser528, and Trp529 while preserving the spatial rigidity of the rest, epitope III in this cocrystal complex adopts a unique conformation that is different from previously described E2 structures. With further analyses of molecular docking and phage display-based peptide interactions, we recognized that it is the arrangements of two separate sets of residues within epitope III that create these discrete conformations for the epitope to interact selectively with either mAb1H8 or CD81. These observations thus raise the possibility that local epitope III conformational dynamics, in conjunction with sequence variations, may act as a regulatory mechanism to coordinate mAb1H8-like antibody-mediated immune defenses with CD81-initiated HCV infections." @default.
• W3181245184 created "2021-07-19" @default.
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• W3181245184 date "2021-07-06" @default.
• W3181245184 modified "2023-10-16" @default.
• W3181245184 title "A conserved epitope III on hepatitis C virus E2 protein has alternate conformations facilitating cell binding or virus neutralization" @default.
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• W3181245184 doi "https://doi.org/10.1073/pnas.2104242118" @default.
• W3181245184 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8285954" @default.
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• W3181245184 hasPublicationYear "2021" @default.
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