2CMR: Crystal structure of the HIV-1 neutralizing antibody D5 Fab bound to the gp41 inner-core mimetic 5-helix

Citation:
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.
PDB ID: 2CMRDownload
MMDB ID: 41963
PDB Deposition Date: 2006/5/11
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Human immunodeficiency virus 1
Similar Structures:
Biological Unit for 2CMR: trimeric; determined by author and by software (PQS)
Molecular Components in 2CMR
Label Count Molecule
Proteins (3 molecules)
1
Transmembrane Glycoprotein
Molecule annotation
1
D5
Molecule annotation
1
D5
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.