4G6F

Crystal Structure of 10E8 Fab in Complex with an HIV-1 gp41 Peptide

Summary for 4G6F

• Entry DOI: 10.2210/pdb4g6f/pdb
• Descriptor: 10E8 Heavy Chain, 10E8 Light Chain, gp41 MPER Peptide, ... (4 entities in total)
• Functional Keywords: immunoglobulin, mper, antibody, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 106130.40

Authors

Ofek, G.,Huang, J.,Connors, M.,Kwong, P.D. (deposition date: 2012-07-19, release date: 2012-09-26, Last modification date: 2024-10-30)

Primary citation

Huang, J.,Ofek, G.,Laub, L.,Louder, M.K.,Doria-Rose, N.A.,Longo, N.S.,Imamichi, H.,Bailer, R.T.,Chakrabarti, B.,Sharma, S.K.,Alam, S.M.,Wang, T.,Yang, Y.,Zhang, B.,Migueles, S.A.,Wyatt, R.,Haynes, B.F.,Kwong, P.D.,Mascola, J.R.,Connors, M.
Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.
Nature, 491:406-412, 2012

PubMed 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 ∼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.

PubMed: 23151583
DOI: 10.1038/nature11544

Experimental method

X-RAY DIFFRACTION (2.1 Å)