title: The impact of influenza hemagglutinin fusion peptide length and viral subtype on its structure and dynamics.
abstract: A peptide comprising no fewer than the first 20 residues of the influenza hemagglutinin HA2 subunit suffices to induce lipid mixing between the membranes of different unilamellar vesicles. This 20-residue peptide was previously reported to adopt an open "boomerang" structure that differs significantly from the closed helical-hairpin structure of a fusion peptide consisting of the first 23 residues of the HA2 sequence. This study investigates the structural and dynamic features of fusion peptides of different length and subtype. Lacking key interactions that stabilize the closed, helical-hairpin structure, the 20-residue peptide is in a dynamic equilibrium between closed and open states, adopting a ca. 11% population of the former when solubilized by DPC micelles. Peptides shorter than 20 residues would have even fewer interactions to stabilize a helical hairpin fold, resulting in a vanishing hairpin population. Considering the conserved nature of hairpin-stabilizing interactions across all serotypes, and the minimum of 20 residues needed for fusion, we postulate that the closed state plays an essential role in the fusion process. However, opening of this hairpin structure may be essential to the formation of a membrane pore at the final stage of the fusion process.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Lorieau
authors.forename: John M
authors.initials: JM
authors.lastname: Louis
authors.forename: Ad
authors.initials: A
authors.lastname: Bax
mesh_terms: D006388:Hemagglutinins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007251:Influenza, Human / Q000821:virology; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D006388:Hemagglutinins; D010446:Peptide Fragments; D014760:Viral Fusion Proteins; D014764:Viral Proteins