5U3K

Crystal Structure of DH511.2 Fab in Complex with HIV-1 gp41 MPER 662-683 Peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.64 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.234 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.

Williams, L.D.Ofek, G.Schatzle, S.McDaniel, J.R.Lu, X.Nicely, N.I.Wu, L.Lougheed, C.S.Bradley, T.Louder, M.K.McKee, K.Bailer, R.T.O'Dell, S.Georgiev, I.S.Seaman, M.S.Parks, R.J.Marshall, D.J.Anasti, K.Yang, G.Nie, X.Tumba, N.L.Wiehe, K.Wagh, K.Korber, B.Kepler, T.B.Munir Alam, S.Morris, L.Kamanga, G.Cohen, M.S.Bonsignori, M.Xia, S.M.Montefiori, D.C.Kelsoe, G.Gao, F.Mascola, J.R.Moody, M.A.Saunders, K.O.Liao, H.X.Tomaras, G.D.Georgiou, G.Haynes, B.F.

(2017) Sci Immunol 2

  • DOI: https://doi.org/10.1126/sciimmunol.aal2200
  • Primary Citation of Related Structures:  
    5U3J, 5U3K, 5U3L, 5U3M, 5U3N, 5U3O, 5U3P

  • PubMed Abstract: 

    Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1-specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1-infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains.


  • Organizational Affiliation

    Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DH511.2 Fab Heavy ChainA [auth H],
C [auth A]
232Homo sapiensMutation(s): 0 
Gene Names: IgG Heavy Chain
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DH511.2 Fab Light ChainB [auth L],
D [auth B]
214Homo sapiensMutation(s): 0 
Gene Names: IgG Light Chain
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
gp41 MPER peptideE [auth P],
F [auth C]
28Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for Q73372 (Human immunodeficiency virus type 1 group M subtype B (strain 89.6))
Explore Q73372 
Go to UniProtKB:  Q73372
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ73372
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.64 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.234 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 109.396α = 90
b = 75.756β = 94.29
c = 122.63γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data collection
HKL-2000data scaling
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 Allergy and Infectious Diseases (NIH/NIAID)United States5UM1AII00645

Revision History  (Full details and data files)

  • Version 1.0: 2017-02-15
    Type: Initial release
  • Version 1.1: 2017-07-05
    Changes: Database references
  • Version 1.2: 2017-08-23
    Changes: Author supporting evidence, Database references, Refinement description
  • Version 1.3: 2019-12-11
    Changes: Author supporting evidence, Derived calculations