The HIV MPER Project

A Duke News article on this work: Tricky Protein May Help HIV Vaccine Development.

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 gp41 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.

We report the design and structure determination of a new antigenic membrane-bound MPER trimer for examining immunogenic responses to the HIV-1 viral coat protein gp41. This new design and structure, called gp41-M-MAT, provides important structural information that can further illuminate HIV vaccine development efforts. Our structure is also an important addition to the relatively small number of multimeric membrane-associated structures determined using solution state NMR.