title: Closed and Semiclosed Interhelical Structures in Membrane vs Closed and Open Structures in Detergent for the Influenza Virus Hemagglutinin Fusion Peptide and Correlation of Hydrophobic Surface Area with Fusion Catalysis.
abstract: The ∼25 N-terminal "HAfp" residues of the HA2 subunit of the influenza virus hemagglutinin protein are critical for fusion between the viral and endosomal membranes at low pH. Earlier studies of HAfp in detergent support (1) N-helix/turn/C-helix structure at pH 5 with open interhelical geometry and N-helix/turn/C-coil structure at pH 7; or (2) N-helix/turn/C-helix at both pHs with closed interhelical geometry. These different structures led to very different models of HAfp membrane location and different models of catalysis of membrane fusion by HAfp. In this study, the interhelical geometry of membrane-associated HAfp is probed by solid-state NMR. The data are well-fitted to a population mixture of closed and semiclosed structures. The two structures have similar interhelical geometries and are planar with hydrophobic and hydrophilic faces. The different structures of HAfp in detergent vs membrane could be due to the differences in interaction with the curved micelle vs flat membrane with better geometric matching between the closed and semiclosed structures and the membrane. The higher fusogenicity of longer sequences and low pH is correlated with hydrophobic surface area and consequent increased membrane perturbation.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
authors.forename: Ujjayini
authors.initials: U
authors.lastname: Ghosh
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
authors.forename: Lihui
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
authors.forename: David P
authors.initials: DP
authors.lastname: Weliky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003902:Detergents / Q000737:chemistry*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006389:Hemagglutinins, Viral / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007251:Influenza, Human / Q000821:virology; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009975:Orthomyxoviridae / Q000737:chemistry*; D009976:Orthomyxoviridae Infections / Q000821:virology; D017433:Protein Structure, Secondary
chemical_list: D003902:Detergents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008823:Micelles; C452559:hemagglutinin HA-2 fusogenic peptide, Influenza virus