skip to main content

Title: A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield

The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man{sub 9} at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short {beta}-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificify. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface.
Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »; ; ; ; ; ; ; ; ; ; ;  [1] ;  [2] ;  [2] ;  [2] ;  [2] ;  [2] ;  [2] ;  [2] « less
  1. (UWASH)
  2. (
Publication Date:
OSTI Identifier:
1030830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Science; Journal Volume: 334; Journal Issue: 11, 2011
Research Org:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Org:
NIHNIAIDFOREIGNOTHER
Country of Publication:
United States
Language:
ENGLISH