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

2011· article· en· 704 citations· W2128579789 on OpenAlex· 10.1126/science.1213256

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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.

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The record

Venue
Science
Topic
HIV Research and Treatment
Field
Immunology and Microbiology
Canadian institutions
Funders
National Center for Research ResourcesNational Institute of General Medical SciencesNational Cancer InstituteCanadian Institutes of Health ResearchEngineering and Physical Sciences Research CouncilNational Institute of Allergy and Infectious Diseases
Keywords
GlycanAntibodyNeutralizationImmunoglobulin Fab FragmentsChemistryBinding siteNeutralizing antibodyVirologyGlycoproteinBiologyImmunoglobulin light chainBiochemistryComplementarity determining regionImmunology
Has abstract in OpenAlex
yes