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-Structure paper
Title | Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. |
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Journal, issue, pages | Cell Rep, Vol. 7, Issue 3, Page 785-795, Year 2014 |
Publish date | May 8, 2014 |
Authors | Louise Scharf / Johannes F Scheid / Jeong Hyun Lee / Anthony P West / Courtney Chen / Han Gao / Priyanthi N P Gnanapragasam / René Mares / Michael S Seaman / Andrew B Ward / Michel C Nussenzweig / Pamela J Bjorkman / |
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, ...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. |
External links | Cell Rep / PubMed:24767986 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.13 - 18.7 Å |
Structure data | EMDB-2625: PDB-4p9h: PDB-4p9m: |
Chemicals | ChemComp-EPE: ChemComp-BEN: ChemComp-NAG: ChemComp-HOH: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / IG FOLD / ANTI HIV / ANTIBODY / IMMUNE SYSTEM COMPLEX / VIRAL PROTEIN-IMMUNE SYSTEM complex / IMMUNE SYSTEM |