3TNM

Crystal structure of A32 Fab, an ADCC mediating anti-HIV-1 antibody


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.190 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding.

Guan, Y.Pazgier, M.Sajadi, M.M.Kamin-Lewis, R.Al-Darmarki, S.Flinko, R.Lovo, E.Wu, X.Robinson, J.E.Seaman, M.S.Fouts, T.R.Gallo, R.C.DeVico, A.L.Lewis, G.K.

(2013) Proc Natl Acad Sci U S A 110: E69-E78

  • DOI: https://doi.org/10.1073/pnas.1217609110
  • Primary Citation of Related Structures:  
    3TNM

  • PubMed Abstract: 

    The HIV-1 envelope glycoprotein (Env) undergoes conformational transitions consequent to CD4 binding and coreceptor engagement during viral entry. The physical steps in this process are becoming defined, but less is known about their significance as targets of antibodies potentially protective against HIV-1 infection. Here we probe the functional significance of transitional epitope exposure by characterizing 41 human mAbs specific for epitopes exposed on trimeric Env after CD4 engagement. These mAbs recognize three epitope clusters: cluster A, the gp120 face occluded by gp41 in trimeric Env; cluster B, a region proximal to the coreceptor-binding site (CoRBS) and involving the V1/V2 domain; and cluster C, the coreceptor-binding site. The mAbs were evaluated functionally by antibody-dependent, cell-mediated cytotoxicity (ADCC) and for neutralization of Tiers 1 and 2 pseudoviruses. All three clusters included mAbs mediating ADCC. However, there was a strong potency bias for cluster A, which harbors at least three potent ADCC epitopes whose cognate mAbs have electropositive paratopes. Cluster A epitopes are functional ADCC targets during viral entry in an assay format using virion-sensitized target cells. In contrast, only cluster C contained epitopes that were recognized by neutralizing mAbs. There was significant diversity in breadth and potency that correlated with epitope fine specificity. In contrast, ADCC potency had no relationship with neutralization potency or breadth for any epitope cluster. Thus, Fc-mediated effector function and neutralization coselect with specificity in anti-Env antibody responses, but the nature of selection is distinct for these two antiviral activities.


  • Organizational Affiliation

    Division of Basic Science and Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fab heavy chain of human anti-HIV-1 Env antibody A32A [auth H],
C [auth A]
231Homo sapiensMutation(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
Fab light chain of human anti-HIV-1 Env antibody A32B [auth L],
D [auth B]
216Homo sapiensMutation(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: 1.85 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.190 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.78α = 103.69
b = 71.316β = 104.02
c = 77.673γ = 105.4
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-09-26
    Type: Initial release
  • Version 1.1: 2015-10-14
    Changes: Database references
  • Version 1.2: 2021-04-21
    Changes: Derived calculations, Source and taxonomy