title: Unusual titration of the membrane-bound artificial hemagglutinin fusion peptide.
abstract: E5 is a 20-residue-long analog of the fusion peptide from influenza hemagglutinin (GLFEAIAEFIEGGWEGLIEG). It has been suggested that two of its five glutamates, Glu11and Glu15, are critical in its pH-dependent membrane perturbation. To reveal their specific involvement, a pair of analogs with substitution of either Glu11 or Glu15 for Ala were synthesized. By analysis of the pH-dependence of the chemical shifts of protons of these peptides bound to dodecylphosphocholine micelles we found: (1) the peptides adopt an amphiphilic alpha-helical structure within residues 2-18, similar to the parent peptide; (2) the helix is significantly more disordered at neutral pH than at acidic pH for E5 peptide only; and (3) in E5 and mutant peptides the Glu11 and 15 residues have similar pK                 (a) values, higher than those of the other glutamates. This excludes their mutual interaction in E5, being a source of the elevated pK                 (a) values. We attribute this phenomenon to the presence of minor states caused by deepening of the Glu11 and 15 side-chains in the hydrophobic environment of the membrane. As the mid-pH of membrane-perturbation activity of E5 matches the pK                 (a) value of these glutamates, we conclude their presence contributes to the plasticity of the peptide and determines the pH-dependence of membrane perturbation caused by E5.
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya str., Moscow 117997, Russia. peter@nmr.ru
authors.forename: Peter V
authors.initials: PV
authors.lastname: Dubovskii
mesh_terms: D000409:Alanine / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000737:chemistry; D008823:Micelles; D010455:Peptides / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008823:Micelles; D010455:Peptides; D010767:Phosphorylcholine; D018698:Glutamic Acid; C028810:dodecylphosphocholine; D000409:Alanine