4WHT

Structure of the Hepatitis C virus envelope glycoprotein E2 antigenic region 412-423 bound to the broadly neutralizing antibody 3/11, P1 crystal form

4WHT の概要

• エントリーDOI: 10.2210/pdb4wht/pdb
• 分子名称: Heavy chain of the Fab fragment derived from neutralizing antibody 3/11, Light chain of the Fab fragment derived from neutralizing antibody 3/11, Epitope peptide, ... (4 entities in total)
• 機能のキーワード: neutralizing epitope, envelope glycoprotein, e2, receptor-binding, viral protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 36
• 化学式量合計: 626242.03

構造登録者

Krey, T.,Rey, F.A. (登録日: 2014-09-23, 公開日: 2014-12-17, 最終更新日: 2024-10-09)

主引用文献

Meola, A.,Tarr, A.W.,England, P.,Meredith, L.W.,McClure, C.P.,Foung, S.K.,McKeating, J.A.,Ball, J.K.,Rey, F.A.,Krey, T.
Structural flexibility of a conserved antigenic region in hepatitis C virus glycoprotein e2 recognized by broadly neutralizing antibodies.
J.Virol., 89:2170-2181, 2015

PubMed Abstract: Neutralizing antibodies (NAbs) targeting glycoprotein E2 are important for the control of hepatitis C virus (HCV) infection. One conserved antigenic site (amino acids 412 to 423) is disordered in the reported E2 structure, but a synthetic peptide mimicking this site forms a β-hairpin in complex with three independent NAbs. Our structure of the same peptide in complex with NAb 3/11 demonstrates a strikingly different extended conformation. We also show that residues 412 to 423 are essential for virus entry but not for E2 folding. Together with the neutralizing capacity of the 3/11 Fab fragment, this indicates an unexpected structural flexibility within this epitope. NAbs 3/11 and AP33 (recognizing the extended and β-hairpin conformations, respectively) display similar neutralizing activities despite converse binding kinetics. Our results suggest that HCV utilizes conformational flexibility as an immune evasion strategy, contributing to the limited immunogenicity of this epitope in patients, similar to the conformational flexibility described for other enveloped and nonenveloped viruses.

PubMed: 25473061
DOI: 10.1128/JVI.02190-14

実験手法

X-RAY DIFFRACTION (2.22 Å)