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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.62 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


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Literature

Structural flexibility of a conserved antigenic region in hepatitis C virus glycoprotein e2 recognized by broadly neutralizing antibodies.

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.

(2015) J Virol 89: 2170-2181

  • DOI: https://doi.org/10.1128/JVI.02190-14
  • Primary Citation of Related Structures:  
    4WHT, 4WHY

  • 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.


  • Organizational Affiliation

    Institut Pasteur, Unité de Virologie Structurale, Department Virologie, Paris, France CNRS UMR 3569, Paris, France.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
epitope peptide
A, B, C, D
12Hepacivirus hominisMutation(s): 0 
UniProt
Find proteins for Q9WJJ4 (Hepacivirus hominis)
Explore Q9WJJ4 
Go to UniProtKB:  Q9WJJ4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9WJJ4
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Heavy chain of Fab fragment derived from neutralizing antibody 3/11E [auth G],
G [auth I],
I [auth K],
K [auth M]
252Rattus norvegicusMutation(s): 0 
Gene Names: IgG
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Light chain of Fab fragment derived from neutralizing antibody 3/11F [auth H],
H [auth J],
J [auth L],
L [auth N]
220Rattus norvegicusMutation(s): 0 
Gene Names: IgG
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.62 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.207 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.76α = 90
b = 205.51β = 103.18
c = 69.02γ = 90
Software Package:
Software NamePurpose
PDB_EXTRACTdata extraction
XDSdata reduction
BUSTERrefinement
XSCALEdata scaling
XSCALEdata reduction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
ANRSFrance--

Revision History  (Full details and data files)

  • Version 1.0: 2014-12-17
    Type: Initial release
  • Version 1.1: 2015-02-04
    Changes: Database references