4p9h

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Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057 HIV-1 and soluble CD4 D1D2Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057 HIV-1 and soluble CD4 D1D2

Structural highlights

4p9h is a 4 chain structure with sequence from Homo sapiens and Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD4_HUMAN Accessory protein for MHC class-II antigen/T-cell receptor interaction. May regulate T-cell activation. Induces the aggregation of lipid rafts.

Publication Abstract from PubMed

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.

Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike.,Scharf L, Scheid JF, Lee JH, West AP Jr, Chen C, Gao H, Gnanapragasam PN, Mares R, Seaman MS, Ward AB, Nussenzweig MC, Bjorkman PJ Cell Rep. 2014 May 8;7(3):785-95. doi: 10.1016/j.celrep.2014.04.001. Epub 2014, Apr 24. PMID:24767986[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Scharf L, Scheid JF, Lee JH, West AP Jr, Chen C, Gao H, Gnanapragasam PN, Mares R, Seaman MS, Ward AB, Nussenzweig MC, Bjorkman PJ. Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike. Cell Rep. 2014 May 8;7(3):785-95. doi: 10.1016/j.celrep.2014.04.001. Epub 2014, Apr 24. PMID:24767986 doi:http://dx.doi.org/10.1016/j.celrep.2014.04.001

4p9h, resolution 3.00Å

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OCA