Interaction of a peptide derived from the N-heptad repeat region of gp41 Env ectodomain with model membranes. Modulation of phospholipid phase behavior

The HIV-1 gp41 envelope protein mediates the entry of the virus into the target cell by promoting membrane fusion. With a view toward possible new insights into the protein membrane alteration leading to the viral fusion mechanism, we have studied by infrared and fluorescence spectroscopies a fragment of 21 amino acids corresponding to the N-heptad repeat region of the gp41 ectodomain. 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. Here we demonstrate that the peptide binds to and interacts with phospholipid model membranes, changing its conformation and inducing leakage of vesicle contents. These characteristics suggest that different specific regions of gp41 are capable of modifying the biophysical properties of phospholipid membranes and, therefore, might be essential for the assistance and enhancement of the viral and cell fusion process.