Structure and interaction with membrane model systems of a peptide derivedfrom the major epitope region of HIV protein gp41: Implications on viral fusion mechanism

The HIV-1 gp41 envelope protein mediates entry of the virus into the target cell by promoting membrane fusion. With a view toward possible new insight s into viral fusion mechanisms, we have investigated by infrared, fluoresce nce, and nuclear magnetic resonance spectroscopies and calorimetry a fragme nt of 19 amino acids corresponding to the immunodominant region of the gp41 ectodomain, a highly conserved sequence and major epitope, Information on the structure of the peptide both in solution and in the presence of model membranes, its incorporation and location in the phospholipid bilayer, and the modulation of the phase behavior of the membrane has been gathered. Her e we demonstrate that the peptide binds and interacts with negatively charg ed phospholipids, changes its conformation in the presence of a membraneous medium, and induces leakage of vesicle contents as well as a new phospholi pid phase. These characteristics might be important for the formation of th e fusion-active gp41 core structure, promoting the close apposition of the two viral and target-cell membranes and therefore provoking fusion.