6BZV

Structure of the Hepatitis C virus envelope glycoprotein E2 antigenic region 412-423 bound to the GL precursor of the broadly neutralizing antibody 19B3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors.

Aleman, F.Tzarum, N.Kong, L.Nagy, K.Zhu, J.Wilson, I.A.Law, M.

(2018) Proc Natl Acad Sci U S A 115: 7569-7574

  • DOI: https://doi.org/10.1073/pnas.1802378115
  • Primary Citation of Related Structures:  
    6BZU, 6BZV, 6BZW, 6BZY

  • PubMed Abstract: 

    Elicitation of broadly neutralizing antibodies (bnAbs) is a leading strategy in rational vaccine design against antigenically diverse pathogens. Here, we studied a panel of monoclonal antibodies (mAbs) from mice immunized with the hepatitis C virus (HCV) envelope glycoproteins E1E2. Six of the mAbs recognize the conserved E2 antigenic site 412-423 (AS412) and cross-neutralize diverse HCV genotypes. Immunogenetic and structural analysis revealed that the antibodies originated from two different germline (GL) precursors and bind AS412 in a β-hairpin conformation. Intriguingly, the anti-HCV activity of one antibody lineage is associated with maturation of the light chain (LC), whereas the other lineage is dependent on heavy-chain (HC) maturation. Crystal structures of GL precursors of the LC-dependent lineage in complex with AS412 offer critical insights into the maturation process of bnAbs to HCV, providing a scientific foundation for utilizing the mouse model to study AS412-targeting vaccine candidates.


  • Organizational Affiliation

    Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
19B3 GL Heavy ChainA [auth E],
C [auth A],
E [auth C],
G
223Mus musculusMutation(s): 0 
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
19B3 GL Light ChainB [auth F],
D [auth B],
F [auth D],
H
219Mus musculusMutation(s): 0 
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
E2 AS412 peptide
I, J, K, L
13Hepacivirus hominisMutation(s): 0 
UniProt
Find proteins for P27958 (Hepatitis C virus genotype 1a (isolate H77))
Explore P27958 
Go to UniProtKB:  P27958
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27958
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.128α = 90
b = 124.767β = 91.42
c = 102.407γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
Blu-Icedata collection

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI106005
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI123365

Revision History  (Full details and data files)

  • Version 1.0: 2018-06-20
    Type: Initial release
  • Version 1.1: 2018-07-11
    Changes: Data collection, Database references
  • Version 1.2: 2018-07-25
    Changes: Data collection, Database references
  • Version 1.3: 2019-02-20
    Changes: Author supporting evidence, Data collection
  • Version 1.4: 2019-12-18
    Changes: Author supporting evidence
  • Version 1.5: 2022-02-02
    Changes: Database references, Structure summary