4Q2Z

Fab fragment of HIV vaccine-elicited CD4bs-directed antibody, GE356, from a non-human primate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.234 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

HIV-1 Receptor Binding Site-Directed Antibodies Using a VH1-2 Gene Segment Orthologue Are Activated by Env Trimer Immunization.

Navis, M.Tran, K.Bale, S.Phad, G.E.Guenaga, J.Wilson, R.Soldemo, M.McKee, K.Sundling, C.Mascola, J.Li, Y.Wyatt, R.T.Karlsson Hedestam, G.B.

(2014) PLoS Pathog 10: e1004337-e1004337

  • DOI: https://doi.org/10.1371/journal.ppat.1004337
  • Primary Citation of Related Structures:  
    4Q2Z

  • PubMed Abstract: 

    Broadly neutralizing antibodies (bNAbs) isolated from chronically HIV-1 infected individuals reveal important information regarding how antibodies target conserved determinants of the envelope glycoprotein (Env) spike such as the primary receptor CD4 binding site (CD4bs). Many CD4bs-directed bNAbs use the same heavy (H) chain variable (V) gene segment, VH1-2*02, suggesting that activation of B cells expressing this allele is linked to the generation of this type of Ab. Here, we identify the rhesus macaque VH1.23 gene segment to be the closest macaque orthologue to the human VH1-2 gene segment, with 92% homology to VH1-2*02. Of the three amino acids in the VH1-2*02 gene segment that define a motif for VRC01-like antibodies (W50, N58, flanking the HCDR2 region, and R71), the two identified macaque VH1.23 alleles described here encode two. We demonstrate that immunization with soluble Env trimers induced CD4bs-specific VH1.23-using Abs with restricted neutralization breadth. Through alanine scanning and structural studies of one such monoclonal Ab (MAb), GE356, we demonstrate that all three HCDRs are involved in neutralization. This contrasts to the highly potent CD4bs-directed VRC01 class of bNAb, which bind Env predominantly through the HCDR2. Also unlike VRC01, GE356 was minimally modified by somatic hypermutation, its light (L) chain CDRs were of average lengths and it displayed a binding footprint proximal to the trimer axis. These results illustrate that the Env trimer immunogen used here activates B cells encoding a VH1-2 gene segment orthologue, but that the resulting Abs interact distinctly differently with the HIV-1 Env spike compared to VRC01.


  • Organizational Affiliation

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heavy chain of Fab fragment of HIV vaccine-elicited CD4bs-directed antibodyA [auth H],
C [auth A]
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
Light chain of Fab fragment of HIV vaccine-elicited CD4bs-directed antibodyB [auth L],
D [auth B]
212Macaca 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: 1.93 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.234 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.243α = 92.39
b = 67.909β = 94.13
c = 69.98γ = 109.69
Software Package:
Software NamePurpose
JBluIce-EPICSdata collection
PHENIXmodel building
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-09-17
    Type: Initial release
  • Version 1.1: 2023-09-20
    Changes: Data collection, Database references, Refinement description