2cmr

File:2cmr.gif

spinqualitylabelsall models 2cmr, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF THE HIV-1 NEUTRALIZING ANTIBODY D5 FAB BOUND TO THE GP41 INNER-CORE MIMETIC 5-HELIX

OverviewOverview

Elicitation of potent and broadly neutralizing antibodies is an important, goal in designing an effective human immunodeficiency virus-1 (HIV-1), vaccine. The HIV-1 gp41 inner-core trimer represents a functionally and, structurally conserved target for therapeutics. Here we report the, 2.0-A-resolution crystal structure of the complex between the, antigen-binding fragment of D5, an HIV-1 cross-neutralizing antibody, and, 5-helix, a gp41 inner-core mimetic. Both binding and neutralization depend, on residues in the D5 CDR H2 loop protruding into the conserved gp41, hydrophobic pocket, as well as a large pocket in D5 surrounding core gp41, residues. Kinetic analysis of D5 mutants with perturbed D5-gp41, interactions suggests that D5 persistence at the fusion intermediate is, crucial for neutralization. Thus, our data validate the gp41 N-peptide, trimer fusion intermediate as a target for neutralizing antibodies and, provide a template for identification of more potent and broadly, neutralizing molecules.

About this StructureAbout this Structure

2CMR is a Single protein structure of sequence from Homo sapiens and Human immunodeficiency virus 1 with GOL as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody., Luftig MA, Mattu M, Di Giovine P, Geleziunas R, Hrin R, Barbato G, Bianchi E, Miller MD, Pessi A, Carfi A, Nat Struct Mol Biol. 2006 Aug;13(8):740-7. Epub 2006 Jul 23. PMID:16862157

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