Structure and topology of the influenza virus fusion peptide in lipid bilayers.
The secondary structure of a 20-amino acid length synthetic peptide corresponding to the N terminus of the second subunit of hemagglutinin (HA2) of influenza virus A/PR8/34 and its interaction with phospholipid bilayers are investigated using ESR, Fourier transform infrared (FTIR), and CD spectroscopy. N-terminal spin labeling of the peptide did not affect the secondary structure of the peptide either in solution or when bound to liposomes as revealed by FTIR and CD spectroscopy. ESR spectra show that the mobility of the labeled peptide is dramatically restricted in the presence of phosphatidylcholine liposomes, suggesting a strong binding to the lipid membranes. The N terminus of the peptide penetrates into the membrane and is located within the hydrophobic core. We find an oblique insertion of the peptide into the lipid bilayer with an angle of about 45 degrees between helix axis and membrane plane using FTIR spectroscopy. No gross changes of the peptide's orientation, motion, and secondary structure were observed between pH 7.4 and pH 5.0. A model of the insertion of the fusion sequence of HA2 into a lipid bilayer is presented taking into account recent investigations on the low pH conformation of HA2 (Bullough, P. A., Hughson, F. M., Skehel, J. J., and Wiley, D. C. (1994) Nature 371, 37-43).
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004578:Electron Spin Resonance Spectroscopy; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000737:chemistry*; D006801:Humans; D009980:Influenza A virus; D008051:Lipid Bilayers; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D017433:Protein Structure, Secondary; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D014759:Viral Envelope Proteins / Q000737:chemistry
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008051:Lipid Bilayers; D010446:Peptide Fragments; D012997:Solvents; D014759:Viral Envelope Proteins