The amino-terminal region of the fusion peptide of influenza virus hemagglutinin HA2 inserts into sodium dodecyl sulfate micelle with residues 16-18 at the aqueous boundary at acidic pH. Oligomerization and the conformational flexibility.

The conformation and interactions with membrane mimics of the NH(2)-terminal fragment 1-25 of HA2, HA2-(1-25), of influenza virus were studied by spectroscopic methods. Secondary structure analysis of circular dichroism data revealed 45% helix for the peptide at pH 5.0. Tryptophan fluorescence quenching by acrylamide and NMR experiments established that the Trp(14) is inside the vesicular interior and residues 16-18 are at the micellar aqueous boundary. NBD fluorescence enhancement of the NH(2)-terminal labeled fluorophore on the vesicle-bound peptide indicated that the NH(2) terminus of the fusion peptide was located in the hydrophobic region of the lipid bilayer. No significant change in insertion depth was observed between pH 5.0 and 7.4. Collectively, these spectroscopic measurements pointed to an equilibrium between helix and non-helix conformations, with helix being the dominant form, for the segment in the micellar interior. The conformational transition may be facilitated by the high content of glycine, a conformationally flexible amino acid, within the fusion peptide sequence. Self-association of the 25-mer peptide was observed in the N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine SDS-gel electrophoresis experiments. Incorporating the NMR signal attenuation, fluorescence, and gel electrophoresis data, a working model for the organization of the fusion peptide in membrane bilayers was proposed.