6MEG

Crystal structure of human monoclonal antibody HEPC46

  • Classification: IMMUNE SYSTEM
  • Organism(s): Homo sapiens
  • Expression System: Homo sapiens
  • Mutation(s): No 

  • Deposited: 2018-09-06 Released: 2018-11-21 
  • Deposition Author(s): Flyak, A.I., Bjorkman, P.J.
  • Funding Organization(s): National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.41 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report

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This is version 1.4 of the entry. See complete history


Literature

HCV Broadly Neutralizing Antibodies Use a CDRH3 Disulfide Motif to Recognize an E2 Glycoprotein Site that Can Be Targeted for Vaccine Design.

Flyak, A.I.Ruiz, S.Colbert, M.D.Luong, T.Crowe Jr., J.E.Bailey, J.R.Bjorkman, P.J.

(2018) Cell Host Microbe 24: 703-716.e3

  • DOI: https://doi.org/10.1016/j.chom.2018.10.009
  • Primary Citation of Related Structures:  
    6MED, 6MEE, 6MEF, 6MEG, 6MEH, 6MEI, 6MEJ, 6MEK

  • PubMed Abstract: 

    Hepatitis C virus (HCV) vaccine efforts are hampered by the extensive genetic diversity of HCV envelope glycoproteins E1 and E2. Structures of broadly neutralizing antibodies (bNAbs) (e.g., HEPC3, HEPC74) isolated from individuals who spontaneously cleared HCV infection facilitate immunogen design to elicit antibodies against multiple HCV variants. However, challenges in expressing HCV glycoproteins previously limited bNAb-HCV structures to complexes with truncated E2 cores. Here we describe crystal structures of full-length E2 ectodomain complexes with HEPC3 and HEPC74, revealing lock-and-key antibody-antigen interactions, E2 regions (including a target of immunogen design) that were truncated or disordered in E2 cores, and an antibody CDRH3 disulfide motif that exhibits common interactions with a conserved epitope despite different bNAb-E2 binding orientations. The structures display unusual features relevant to common genetic signatures of HCV bNAbs and demonstrate extraordinary plasticity in antibody-antigen interactions. In addition, E2 variants that bind HEPC3/HEPC74-like germline precursors may represent candidate vaccine immunogens.


  • Organizational Affiliation

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
antibody HEPC46 Heavy ChainA [auth H]230Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
antibody HEPC46 Light ChainB [auth L]217Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.41 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.64α = 90
b = 71.302β = 90
c = 108.59γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
MOSFLMdata reduction
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI127469

Revision History  (Full details and data files)

  • Version 1.0: 2018-11-21
    Type: Initial release
  • Version 1.1: 2018-11-28
    Changes: Data collection, Database references
  • Version 1.2: 2019-11-06
    Changes: Data collection, Structure summary
  • Version 1.3: 2019-12-18
    Changes: Author supporting evidence
  • Version 1.4: 2023-10-11
    Changes: Data collection, Database references, Refinement description