4P9H

Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057 HIV-1 and soluble CD4 D1D2

Summary for 4P9H

• Entry DOI: 10.2210/pdb4p9h/pdb
• Descriptor: T-cell surface glycoprotein CD4, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, BENZAMIDINE, ... (12 entities in total)
• Functional Keywords: ig fold, anti hiv, antibody, immune system complex, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 117366.92

Authors

Scharf, L.,Bjorkman, P.J. (deposition date: 2014-04-04, release date: 2014-05-21, Last modification date: 2024-10-23)

Primary citation

Scharf, L.,Scheid, J.F.,Lee, J.H.,West, A.P.,Chen, C.,Gao, H.,Gnanapragasam, P.N.,Mares, R.,Seaman, M.S.,Ward, A.B.,Nussenzweig, M.C.,Bjorkman, P.J.
Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike.
Cell Rep, 7:785-795, 2014

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, are currently limited. We defined a new site of vulnerability by solving structures of bNAb 8ANC195 complexed with monomeric gp120 by X-ray crystallography and trimeric Env by electron microscopy. The site includes portions of gp41 and N-linked glycans adjacent to the CD4-binding site on gp120, making 8ANC195 the first donor-derived anti-HIV-1 bNAb with an epitope spanning both Env subunits. Rather than penetrating the glycan shield by using a single variable-region CDR loop, 8ANC195 inserted its entire heavy-chain variable domain into a gap to form a large interface with gp120 glycans and regions of the gp120 inner domain not contacted by other bNAbs. By isolating additional 8ANC195 clonal variants, we identified a more potent variant, which may be valuable for therapeutic approaches using bNAb combinations with nonoverlapping epitopes.

PubMed: 24767986
DOI: 10.1016/j.celrep.2014.04.001

Experimental method

X-RAY DIFFRACTION (3 Å)