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A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield.

TitleA potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield.
Publication TypeJournal Article
Year of Publication2011
AuthorsPejchal R, Doores KJ, Walker LM, Khayat R, Huang P-S, Wang S-K, Stanfield RL, Julien J-P, Ramos A, Crispin M, Depetris R, Katpally U, Marozsan A, Cupo A, Maloveste S, Liu Y, McBride R, Ito Y, Sanders RW, Ogohara C, Paulson JC, Feizi T, Scanlan CN, Wong C-H, Moore JP, Olson WC, Ward AB, Poignard P, Schief WR, Burton DR, Wilson IA
JournalScience
Volume334
Issue6059
Pagination1097-103
Date Published2011 Nov 25
ISSN1095-9203
KeywordsAntibodies, Neutralizing, Antibody Specificity, Binding Sites, Antibody, Carbohydrate Conformation, Cell Line, Crystallography, X-Ray, Disaccharides, Epitopes, Glycosylation, HIV Antibodies, HIV Envelope Protein gp120, HIV-1, Humans, Hydrogen Bonding, Immunoglobulin Fab Fragments, Mannose, Mannosides, Models, Molecular, Mutation, Oligosaccharides, Polysaccharides, Protein Conformation, Protein Structure, Tertiary
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.

DOI10.1126/science.1213256
Alternate JournalScience
PubMed ID21998254
PubMed Central IDPMC3280215
Grant ListAI082362 / AI / NIAID NIH HHS / United States
AI33292 / AI / NIAID NIH HHS / United States
AI74372 / AI / NIAID NIH HHS / United States
AI84817 / AI / NIAID NIH HHS / United States
F32 AI074372-03 / AI / NIAID NIH HHS / United States
HFE-224662 / / Canadian Institutes of Health Research / Canada
P01 AI082362 / AI / NIAID NIH HHS / United States
P01 AI082362-03 / AI / NIAID NIH HHS / United States
P01 AI082362-04 / AI / NIAID NIH HHS / United States
P41RR001209 / RR / NCRR NIH HHS / United States
R01 AI033292 / AI / NIAID NIH HHS / United States
R01 AI033292-14 / AI / NIAID NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
R01 AI084817-04 / AI / NIAID NIH HHS / United States
RR017573 / RR / NCRR NIH HHS / United States
U01 CA128416 / CA / NCI NIH HHS / United States
Y1-CO-1020 / CO / NCI NIH HHS / United States
Y1-GM-1104 / GM / NIGMS NIH HHS / United States

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