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

By R. Pejchal, K. Doores, L. Walker, R. Khayat, Po-Ssu Huang, Sheng-Kai Wang, R. Stanfield, J. Julien, Alejandra Ramos, M. Crispin and 21 more. Science, 2011

731 citations recorded by the source corpus.

An HIV antibody achieves potency and breadth by binding simultaneously to two conserved glycans on the viral envelope protein. 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 Man9 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 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.

Subfields: Molecular Biology, Radiology, Nuclear Medicine and Imaging, Virology

View Paper: https://www.semanticscholar.org/paper/aa548dec22c9f21be7de655fc0b64ba30d143cf9

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Citations in the corpus

Growing Glycans in Rosetta: Accurate de novo glycan modeling, density fitting, and rational sequon design (2021, background): “Yet, HIV broadly neutralizing antibodies often target glycans as part of their epitopes [3] [4] [5].”
Crystal structure of a soluble cleaved HIV-1 envelope trimer (2013, background): “Whereas the PGT128 heavy chain predominantly interacts with the gp120 V3 base, PGT122 recognizes this region mainly through its light chain.”
Neutralization of influenza A viruses by insertion of a single antibody loop into the receptor binding site (2012, neutral): “The experiments comprised five steps: (1) baseline acquisition (60 s); (2) HA loading onto sensor (300–600 s); (3) second baseline acquisition (180–200 s); (4) association of C05 for the measurement of kon (180 s); and (5) dissociation of C05 for themeasurement of koff (180 s).”
A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies (2013, methodology): “664 gp140 trimers have already been already useful for structure-based studies aimed at defining bNAbEnv interactions [25,26,27], as were the corresponding trimers based on the KNH1144 env gene [46,48,60].”
Biological roles of glycans (2016, background): “Sometimes, such protective glycosylation can become so dense that it generates unique clustered epitopes recognized by specific antibodies, such as that seen on the surface of the HIV virion (507) (508) (509) 594) .”