2CMR

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

Summary for 2CMR

• Entry DOI: 10.2210/pdb2cmr/pdb
• Related: 1AIK 1DF4 1DF5 1DLB 1G9M 1GC1 1GZL 1K33 1K34 1MZI 1OPN 1OPT 1OPW 1RZJ
• Descriptor: TRANSMEMBRANE GLYCOPROTEIN, D5, GLYCEROL, ... (5 entities in total)
• Functional Keywords: immune system, immunoglobulin complex, neutralization, immunoglobulin, envelope protein, hiv, gp41, aids, mhc i, membrane, transmembrane, immunoglobulin domain
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS 1; More
• Total number of polymer chains: 3
• Total formula weight: 71017.23

Authors

Luftig, M.A.,Mattu, M.,Di Giovine, P.,Geleziunas, R.,Hrin, R.,Barbato, G.,Bianchi, E.,Miller, M.D.,Pessi, A.,Carfi, A. (deposition date: 2006-05-11, release date: 2006-10-16, Last modification date: 2024-11-13)

Primary citation

Luftig, M.A.,Mattu, M.,Di Giovine, P.,Geleziunas, R.,Hrin, R.,Barbato, G.,Bianchi, E.,Miller, M.D.,Pessi, A.,Carfi, A.
Structural Basis for HIV-1 Neutralization by a Gp41 Fusion Intermediate-Directed Antibody
Nat.Struct.Mol.Biol., 13:740-, 2006

PubMed 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.

PubMed: 16862157
DOI: 10.1038/NSMB1127

Experimental method

X-RAY DIFFRACTION (2 Å)