5I8C

Crystal Structure of HIV-1 Clade A BG505 Fusion Peptide (residue 512-520) in Complex with Broadly Neutralizing Antibody VRC34.01 Fab


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.161 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.

Kong, R.Xu, K.Zhou, T.Acharya, P.Lemmin, T.Liu, K.Ozorowski, G.Soto, C.Taft, J.D.Bailer, R.T.Cale, E.M.Chen, L.Choi, C.W.Chuang, G.Y.Doria-Rose, N.A.Druz, A.Georgiev, I.S.Gorman, J.Huang, J.Joyce, M.G.Louder, M.K.Ma, X.McKee, K.O'Dell, S.Pancera, M.Yang, Y.Blanchard, S.C.Mothes, W.Burton, D.R.Koff, W.C.Connors, M.Ward, A.B.Kwong, P.D.Mascola, J.R.

(2016) Science 352: 828-833

  • DOI: https://doi.org/10.1126/science.aae0474
  • Primary Citation of Related Structures:  
    5I8C, 5I8E, 5I8H

  • PubMed Abstract: 

    The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.


  • Organizational Affiliation

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
VRC34.01 Fab heavy chain223Homo sapiensMutation(s): 0 
Gene Names: IGHG1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
VRC34.01 Fab light chain212Homo sapiensMutation(s): 0 
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HIV-1 Clade A BG505 Fusion Peptide (residue 512-520)9Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for Q2N0S7 (Human immunodeficiency virus 1)
Explore Q2N0S7 
Go to UniProtKB:  Q2N0S7
Entity Groups  
UniProt GroupQ2N0S7
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.161 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.471α = 90
b = 74.895β = 90
c = 84.462γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
HKL-2000data scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States--

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-25
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.2: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Refinement description