Structure of the membrane proximal external region of HIV-1 envelope glycoprotein

The conserved, membrane-proximal external region (MPER) of the HIV-1 envelope glycoprotein (Env) is a potential vaccine target. To visualize its structure in the context of a lipid-bilayer membrane, we have reconstituted a polypeptide containing the HIV-1 MPER and the contiguous transmembrane domain into a bilayer-like environment and determined its atomic structure by NMR. The MPER folds into a trimeric cluster, well exposed on the bilayer surface, even in the absence of the structural constraints from the rest of the Env ectodomain. Our analyses suggest that this structure probably represents a prefusion conformation of the MPER. The findings imply that presenting a well-defined structure will be important for MPER-based immunogen design.