Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120

 
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Kong, Leopold
Lee, Jeong Hyun
Doores, Katie J.
Murin, Charles D.
Julien, Jean-Philippe
McBride, Ryan
Liu, Yan
Marozsan, Andre
Cupo, Albert
Klasse, Per-Johan
Hoffenberg, Simon
Caulfield, Michael
King, C. Richter
Hua, Yuanzi
Le, Khoa M.
Khayat, Reza
Deller, Marc C.
Clayton, Thomas
Tien, Henry
Feizi, Ten
Sanders, Rogier W.
Paulson, James C.
Moore, John P.
Stanfield, Robyn L.
Burton, Dennis R.
Ward, Andrew B.
Wilson, Ian A.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nsmb.2594
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Kong, L., J. H. Lee, K. J. Doores, C. D. Murin, J. Julien, R. McBride, Y. Liu, et al. 2013. “Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120.” Nature structural & molecular biology 20 (7): 10.1038/nsmb.2594. doi:10.1038/nsmb.2594. http://dx.doi.org/10.1038/nsmb.2594.
Abstract
A substantial fraction of broadly neutralizing antibodies (bnAbs) in certain HIV-infected donors recognizes glycan-dependent epitopes on HIV-1 gp120. Here, we elucidate how bnAb PGT 135 recognizes its Asn332 glycan-dependent epitope from its crystal structure with gp120, CD4 and Fab 17b at 3.1 Å resolution. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield to access the gp120 protein surface. Electron microscopy reveals PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. The combined structural studies of PGT 135, PGT 128 and 2G12 show this Asn332-dependent epitope is highly accessible and much more extensive than initially appreciated, allowing for multiple binding modes and varied angles of approach, thereby representing a supersite of vulnerability for antibody neutralization.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823233/pdf/
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879685

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