3TWC

Crystal structure of broad and potent HIV-1 neutralizing antibody PGT127 in complex with Man9

Summary for 3TWC

• Entry DOI: 10.2210/pdb3twc/pdb
• Related: 3TV3 3TYG
• Descriptor: PGT127 light chain, Ig lambda-2 chain C regions, PGT127 heavy chain, Ig gamma-1 chain C region, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose, ... (5 entities in total)
• Functional Keywords: fab, hiv-1 neutralizing antibody, gp120, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 49452.81

Authors

Pejchal, R.,Wilson, I.A. (deposition date: 2011-09-21, release date: 2011-10-19, Last modification date: 2024-10-16)

Primary citation

Pejchal, R.,Doores, K.J.,Walker, L.M.,Khayat, R.,Huang, P.S.,Wang, S.K.,Stanfield, R.L.,Julien, J.P.,Ramos, A.,Crispin, M.,Depetris, R.,Katpally, U.,Marozsan, A.,Cupo, A.,Maloveste, S.,Liu, Y.,McBride, R.,Ito, Y.,Sanders, R.W.,Ogohara, C.,Paulson, J.C.,Feizi, T.,Scanlan, C.N.,Wong, C.H.,Moore, J.P.,Olson, W.C.,Ward, A.B.,Poignard, P.,Schief, W.R.,Burton, D.R.,Wilson, I.A.
A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield.
Science, 334:1097-1103, 2011

PubMed 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.

PubMed: 21998254
DOI: 10.1126/science.1213256

Experimental method

X-RAY DIFFRACTION (1.65 Å)