4G6F: Crystal Structure of 10e8 FAB in Complex With an Hiv-1 Gp41 Peptide

Citation:
Abstract
Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes approximately 98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.
PDB ID: 4G6FDownload
MMDB ID: 103370
PDB Deposition Date: 2012/7/19
Updated in MMDB: 2012/12 
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Human immunodeficiency virus 1
Similar Structures:
Biological Unit for 4G6F: hexameric; determined by author
Molecular Components in 4G6F
Label Count Molecule
Proteins (6 molecules)
2
10e8 Heavy Chain
Molecule annotation
2
10e8 Light Chain
Molecule annotation
2
Gp41 Mper Peptide
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.