4WHY

Structure of the Hepatitis C virus envelope glycoprotein E2 antigenic region 412-423 bound to the broadly neutralizing antibody 3/11, P21 crystal form

Summary for 4WHY

• Entry DOI: 10.2210/pdb4why/pdb
• Related: 4WHT
• Descriptor: epitope peptide, Heavy chain of Fab fragment derived from neutralizing antibody 3/11, Light chain of Fab fragment derived from neutralizing antibody 3/11, ... (4 entities in total)
• Functional Keywords: neutralizing epitope, envelope glycoprotein, e2, receptor-binding, viral protein
• Biological source: Rattus norvegicus (Norway Rat); More
• Total number of polymer chains: 12
• Total formula weight: 208747.34

Authors

Krey, T.,Rey, F.A. (deposition date: 2014-09-24, release date: 2014-12-17, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.62 Å)