| Literature DB >> 21998254 |
Robert Pejchal1, Katie J Doores, Laura M Walker, Reza Khayat, Po-Ssu Huang, Sheng-Kai Wang, Robyn L Stanfield, Jean-Philippe Julien, Alejandra Ramos, Max Crispin, Rafael Depetris, Umesh Katpally, Andre Marozsan, Albert Cupo, Sebastien Maloveste, Yan Liu, Ryan McBride, Yukishige Ito, Rogier W Sanders, Cassandra Ogohara, James C Paulson, Ten Feizi, Christopher N Scanlan, Chi-Huey Wong, John P Moore, William C Olson, Andrew B Ward, Pascal Poignard, William R Schief, Dennis R Burton, Ian A Wilson.
Abstract
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(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 β-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificity. 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.Entities:
Mesh：
Substances：
Year: 2011 PMID： 21998254 PMCID： PMC3280215 DOI： 10.1126/science.1213256
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728