5DD5

Crystal structures in an anti-HIV antibody lineage from immunization of Rhesus macaques


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.

Zhang, R.Verkoczy, L.Wiehe, K.Munir Alam, S.Nicely, N.I.Santra, S.Bradley, T.Pemble, C.W.Zhang, J.Gao, F.Montefiori, D.C.Bouton-Verville, H.Kelsoe, G.Larimore, K.Greenberg, P.D.Parks, R.Foulger, A.Peel, J.N.Luo, K.Lu, X.Trama, A.M.Vandergrift, N.Tomaras, G.D.Kepler, T.B.Moody, M.A.Liao, H.X.Haynes, B.F.

(2016) Sci Transl Med 8: 336ra62-336ra62

  • DOI: https://doi.org/10.1126/scitranslmed.aaf0618
  • Primary Citation of Related Structures:  
    5DD0, 5DD1, 5DD3, 5DD5, 5DD6

  • PubMed Abstract: 

    Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either deleted or did not attain sufficient affinity for gp41-lipid complexes to achieve the neutralization potency of 2F5. Structural analysis of members of a vaccine-induced antibody lineage revealed that heavy chain complementarity-determining region 3 (HCDR3) hydrophobicity was important for neutralization. Thus, gp41 bnAbs are controlled by immune tolerance, requiring vaccination strategies to transiently circumvent tolerance controls.


  • 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
ANTI-HIV ANTIBODY DH570.9 FAB HEAVY CHAINA [auth H]233Macaca mulattaMutation(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
ANTI-HIV ANTIBODY DH570.9 FAB HEAVY CHAINB [auth L]214Macaca mulattaMutation(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: 1.90 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.202 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.35α = 90
b = 77.43β = 90
c = 138.42γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
PHENIXphasing

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 StatesUM1-AI100645-02

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-11
    Type: Initial release
  • Version 1.1: 2016-05-18
    Changes: Structure summary
  • Version 1.2: 2017-09-20
    Changes: Author supporting evidence, Derived calculations
  • Version 1.3: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.4: 2023-09-27
    Changes: Data collection, Database references, Refinement description