title: Single mutation effects on conformational change and membrane deformation of influenza hemagglutinin fusion peptides.
abstract: The single mutation effect on the conformational change and membrane permeation of influenza hemagglutinin fusion peptides has been studied with molecular dynamics simulations. A total of seven peptides, including wild-type fusion peptide and its six single point mutants (G1E, G1S, G1V, G4V, E11A, and W14A, all with no fusion or hemifusion activity) are examined systematically, which covers a wide range of mutation sites as well as mutant residue types (both hydrophobic and hydrophilic). The wild-type shows a kink structure (inversed V-shape), which facilitates the interaction between the fusion peptide and the lipid bilayer, as well as the interaction between the two arms of the fusion peptide. All mutants show a strong tendency toward a linear alpha-helix conformation, with the initial kink structure in the wild-type broken. More interestingly, one of the key hydrophobic residues around the initial kink region, Phe-9, is found to flip away from the membrane surface in most of these mutants. This conformational change causes a loss of key interactions between the original two arms of the inversed V-shape of the wild-type, thus disabling the kink structure, which results in the stabilization of the linear alpha-helix structure. The fusion peptides also display significant impact on the membrane structure deformation. The thickness of the lipid bilayer surrounding the wild-type fusion peptide decreases significantly, which induces a positive curvature of lipid bilayer. All the single mutations examined here reduce this membrane structural deformation, supporting the fusion activity data from experiments.
authors.affiliation: Department of Physics, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.forename: Payel
authors.initials: P
authors.lastname: Das
authors.forename: Ruhong
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D011487:Protein Conformation; D014760:Viral Fusion Proteins / Q000737:chemistry*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008051:Lipid Bilayers; D010446:Peptide Fragments; D014760:Viral Fusion Proteins