Structure of an HIV-1–neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer

• DOI: 10.1073/pnas.1309842111
• Publication Date: 2014-01-14T02:39:11Z
• Authors: Patrick N. Reardon; Harvey Sage; S. Moses Dennison; Jeffrey W. Martin; Bruce R. Donald; S. Munir Alam; Barton F. Haynes; Leonard D. Spicer
• Keywords: Models, Molecular; 0301 basic medicine; 03 medical and health sciences; Biopolymers; Magnetic Resonance Spectroscopy; Molecular Sequence Data; HIV-1; Amino Acid Sequence; Antibodies, Neutralizing; HIV Envelope Protein gp41; 3. Good health

Significance A major roadblock in the development of an HIV vaccine is the need to develop vaccine regimens that will induce antibodies that bind to conserved regions of the HIV envelope and neutralize many different virus quasispecies. One such envelope target is at the region closest to the membrane, the glycoprotein (gp) 41 membrane proximal external region (MPER). Previous work has demonstrated that antibodies that target this region bind both to the gp41 polypeptide and to the adjacent viral membrane. However, what has been missing is a view of what the MPER-neutralizing epitopes may look like in the context of a trimeric orientation with lipids. We have constructed an MPER trimer associated with lipids and solved the trimer structure by NMR spectroscopy.