Interactions between HIV-1 gp41 core and detergents and their implicationsfor membrane fusion

The gp41 envelope protein mediates entry of human immunodeficiency virus ty pe 1 (HIV-1) into the cell by promoting membrane fusion, The crystal struct ure of a gp41 ectodomain core in its fusion-active state is a six-helix bun dle in which a N-terminal trimeric coiled coil is surrounded by three C-ter minal outer helices in an antiparallel orientation. Here we demonstrate tha t the N34(L6)C28 model of the gp41 core is stabilized by interaction with t he ionic detergent sodium dodecyl sulfate (SDS) or the nonionic detergent n -octyl-beta-D-glucopyranoside (beta OG), The high resolution x-ray structur es of N34(L6)C28 crystallized from two different detergent micellar media r eveal a six-helix bundle conformation very similar to that of the molecule in water. Moreover, N34(L6)C28 adopts a highly alpha-helical conformation i n lipid vesicles. Taken together, these results suggest that the six-helix bundle of the gp41 core displays substantial affinity for lipid bilayers ra ther than unfolding in the membrane environment. This characteristic may be important for formation of the fusion-active gp41 core structure and close apposition of the viral and cellular membranes for fusion.