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

HIV_WT and HIV_V2E represent the 23 amino acids fusion peptide of HIV-1 gp41 N terminus and its position 2 mutant (Val→Glu). We have studied the structure-function relationship of HIV_WT and HIV_V2E when they interact with acidic and neutral lipid membranes. The results show that HIV_WT and HIV_V2E have the same conformational characteristics and tendencies of conformational transition but definitely different functions: HIV_WT destabilizes membrane and induces fusion by adopting predominant α-helix conformation when interacting with acidic POPG membrane, its phenylalanine residues can penetrate into the hydrophobic core of POPG bilayer; HIV_V2E also adopts predominant α-helix when interacting with POPG membrane, but it cannot destabilize POPG membrane and induce fusion, the phenylalanine residues of it are located near the surface of POPG bilayer. HIV_WT and HIV_V2E both adopt predominant β-sheet conformation to interact with neutral POPC membrane, and cannot destabilize POPC membrane and induce fusion, the position of phenylalanine residues of both HIV_WT and HIV_V2E are close to the surface of POPC bilayer. These results demonstrate that the N terminal hydrophobicity of fusion peptide and the secondary structure when interacting with lipid membrane play important roles for fusion peptide exerting its function.