Secondary structure, phospholipid membrane interactions, and fusion activity of two glutamate-rich analogs of influenza hemagglutinin fusion peptide.
Two synthetic mutants of influenza HA2 fusion peptide (residues 1-25), containing Glu on the polar (residues 4,8-E5(4,8)) or the hydrophobic (residues 3,7-E5(3,7)) face of the amphipathic helix, were synthesized and labeled with NBD at the N-terminus. Introduction of Glu residues into the fusion peptide leads to increased sensitivity of various biochemical properties to pH compared to the wild type. The E5 peptides showed a decrease of alpha-helix content and increase of beta-sheet structure. Lipid binding was diminished, but not abolished even at high pH. The E5 analogs penetrate the lipid bilayer less deeply than the wild type, especially at high pH. The N-terminal half of the peptide showed significant variation of the depth of the penetration into the lipid bilayer. Both E5 peptides were fusion active. The properties of E5(3,7) were more affected by the Glu substitution and showed greater variation with pH than E5(4,8).
Kantchev
Eric Assen B
EA
Institute of Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan.
Cheng
Shu-Fang
SF
Wu
Cheng-Wei
CW
Huang
Hung-Jen
HJ
Chang
Ding-Kwo
DK
D001665:Binding Sites; D018698:Glutamic Acid / Q000737:chemistry*; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000145:classification; D008051:Lipid Bilayers / Q000737:chemistry*; D046911:Macromolecular Substances; D008560:Membrane Fluidity; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry*; D008567:Membranes, Artificial; D009154:Mutation; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D006389:Hemagglutinins, Viral; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008567:Membranes, Artificial; D010743:Phospholipids; C452559:hemagglutinin HA-2 fusogenic peptide, Influenza virus; D018698:Glutamic Acid