title: Structure of an analog of fusion peptide from hemagglutinin.
abstract: A 20-residue peptide E5 containing five glutamates, an analog of the fusion peptide of influenza virus hemagglutinin (HA) exhibiting fusion activity at acidic pH lower than 6.0-6.5 was studied by circular dichroism (CD), Fourier transform infrared, and 1H-NMR spectroscopy in water, water/trifluoroethanol (TFE) mixtures, dodecylphosphocholine (DPC) micelles, and phospholipid vesicles. E5 became structurally ordered at pH < or = 6 and the helical content in the peptide increased in the row: water < water/TFE < DPC approximately = phospholipid vesicle while the amount of beta-structure was approximately reverse. 1H-NMR data and line-broadening effect of 5-, 16-doxylstearates on proton resonances of DPC bound peptide showed E5 forms amphiphilic alpha-helix in residues 2-18, which is flexible in 11-18 part. The analysis of the proton chemical shifts of DPC bound and CD intensity at 220 nm of phospholipid bound E5 showed that the pH dependence of helical content is characterized by the same pKa approximately 5.6. Only Glu11 and Glu15 in DPC bound peptide showed such elevated pKas, presumably due to transient hydrogen bond(s) Glu11 (Glu15) deltaCOO- (H+)...HN Glu15 that dispose(s) the side chain of Glu11 (Glu15) residue(s) close to the micelle/water interface. These glutamates are present in the HA-fusion peptide and the experimental half-maximal pH of fusion for HA and E5 peptides is approximately 5.6. Therefore, a specific anchorage of these peptides onto membrane necessary for fusion is likely driven by the protonation of the carboxylate group of Glu11 (Glu15) residue(s) participating in transient hydrogen bond(s).
authors.affiliation: Department of Molecular Science, Graduate School of Science and Technology, Kobe University, Japan.
authors.forename: P V
authors.initials: PV
authors.lastname: Dubovskii
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: A S
authors.initials: AS
authors.lastname: Arseniev
authors.forename: K
authors.initials: K
authors.lastname: Akasaka
mesh_terms: D002942:Circular Dichroism; D006388:Hemagglutinins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D013055:Spectrophotometry, Infrared
chemical_list: D006388:Hemagglutinins; D008823:Micelles; D010455:Peptides; D011993:Recombinant Fusion Proteins