Format

Send to

Choose Destination
Nat Struct Mol Biol. 2006 Aug;13(8):740-7. Epub 2006 Jul 23.

Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody.

Author information

1
Istituto di Ricerche di Biologia Molecolare P. Angeletti, Via Pontina Km 30,600, I-00040 Pomezia (Rome), Italy.

Abstract

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.

PMID:
16862157
DOI:
10.1038/nsmb1127
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center