title: Role of the Glu residues of the influenza hemagglutinin fusion peptide in the pH dependence of fusion activity.
abstract: To elucidate the role of the fusion peptide in influenza hemagglutinin (HA)-mediated fusion, we compared pH-dependent conformational changes and fusion mediated by wild-type and a mutant HA in which Glu residues at positions 11 and 15 of the fusion peptide are substituted for valine. The pH dependence of conformational changes and kinetics of fusion with erythrocytes was the same for both forms of HA. The time for commitment and the temperature dependence of HA-mediated fusion were also the same. However, striking differences were observed between wild-type and mutant fusion peptides in their interactions with lipid membranes at neutral and acidic pH. Since elimination of the negatively charged residues allows the exposed fusion peptide to penetrate the bilayer at pH values closer to neutral, but does not affect conformational changes and fusion activity in intact HA, we conclude that conformational changes are tightly coupled to fusion peptide insertion in the overall HA-mediated fusion cascade.
authors.affiliation: Laboratory of Experimental and Computational Biology, National Institutes of Health, Frederick, Maryland 21702, USA.
authors.forename: T
authors.initials: T
authors.lastname: Korte
authors.forename: R F
authors.initials: RF
authors.lastname: Epand
authors.forename: R M
authors.initials: RM
authors.lastname: Epand
authors.forename: R
authors.initials: R
authors.lastname: Blumenthal
mesh_terms: D016475:3T3 Cells; D019943:Amino Acid Substitution; D000818:Animals; D002459:Cell Fusion; D004912:Erythrocytes / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008561:Membrane Fusion; D008563:Membrane Lipids; D051379:Mice; D009154:Mutation; D011487:Protein Conformation; D013696:Temperature; D013997:Time Factors; D014162:Transfection; D014760:Viral Fusion Proteins / Q000378:metabolism
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008563:Membrane Lipids; D014760:Viral Fusion Proteins; D018698:Glutamic Acid