Interaction of HIV-1 fusion peptide and its mutant with lipid membrane

HIVWT and HIVV2E represent the 23 amino acids fusion peptide of HIV-1 gp41 N terminus and its position 2 mutant (Val-->Glu). We have studied the struc ture-function relationship of HIVWT and HIVV2E when they interact with acid ic and neutral lipid membranes. The results show that HIVWT and HIVV2E have the same conformational characteristics and tendencies of conformational t ransition but definitely different functions: HIVWT destabilizes membrane a nd induces fusion by adopting predominant alpha-helix conformation when int eracting with acidic POPG membrane, its phenylalanine residues can penetrat e into the hydrophobic core of POPG bilayer; HIVV2E also adopts predominant alpha-helix when interacting with POPG membrane, but it cannot destabilize POPG membrane and induce fusion, the phenylalanine residues of it are loca ted near the surface of POPG bilayer. HIVWT and HIVV2E both adopt predomina nt beta-sheet conformation to interact with neutral POPC membrane, and cann ot destabilize POPC membrane and induce fusion, the position of phenylalani ne residues of both HIVWT and HIVV2E are close to the surface of POPC bilay er. These results demonstrate that the N terminal hydrophobicity of fusion peptide and the secondary structure when interacting with lipid membrane pl ay important roles for fusion peptide exerting its function.