5UKP

Structure of unliganded anti-gp120 CD4bs antibody DH522.1 Fab

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

  • Deposited: 2017-01-23 Released: 2017-12-06 
  • Deposition Author(s): Nicely, N.I.
  • Funding Organization(s): National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID), Duke University Center for AIDS Research

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.

Williams, W.B.Zhang, J.Jiang, C.Nicely, N.I.Fera, D.Luo, K.Moody, M.A.Liao, H.X.Alam, S.M.Kepler, T.B.Ramesh, A.Wiehe, K.Holland, J.A.Bradley, T.Vandergrift, N.Saunders, K.O.Parks, R.Foulger, A.Xia, S.M.Bonsignori, M.Montefiori, D.C.Louder, M.Eaton, A.Santra, S.Scearce, R.Sutherland, L.Newman, A.Bouton-Verville, H.Bowman, C.Bomze, H.Gao, F.Marshall, D.J.Whitesides, J.F.Nie, X.Kelsoe, G.Reed, S.G.Fox, C.B.Clary, K.Koutsoukos, M.Franco, D.Mascola, J.R.Harrison, S.C.Haynes, B.F.Verkoczy, L.

(2017) Nat Commun 8: 1732-1732

  • DOI: https://doi.org/10.1038/s41467-017-01336-3
  • Primary Citation of Related Structures:  
    5UKN, 5UKO, 5UKP, 5UKQ, 5UKR

  • PubMed Abstract: 

    A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env + B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env - upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env + (non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools.


  • 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
DH522.1 Fab fragment heavy chainA [auth H]230Macaca 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
DH522.1 Fab fragment light chainB [auth L]216Macaca 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: 2.00 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.682α = 90
b = 70.682β = 90
c = 169.835γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data

  • Released Date: 2017-12-06 
  • Deposition Author(s): Nicely, N.I.

Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesUM1-AI100645
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01-AI087202
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01-AI118571
Duke University Center for AIDS ResearchUnited StatesP30-AI-64518

Revision History  (Full details and data files)

  • Version 1.0: 2017-12-06
    Type: Initial release
  • Version 1.1: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description