4P9M

Crystal structure of 8ANC195 Fab

Summary for 4P9M

• Entry DOI: 10.2210/pdb4p9m/pdb
• Related: 4P9H
• Descriptor: 8ANC195 light chain, 8ANC195 Fab heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: ig fold, anti hiv, antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 49748.46

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 (2.13 Å)