title: Early steps of the conformational change of influenza virus hemagglutinin to a fusion active state: stability and energetics of the hemagglutinin.
abstract: A conformational change of the homotrimeric glycoprotein hemagglutinin (HA) of influenza virus mediates fusion between the viral envelope and the endosome membrane. The conformational change of the HA ectodomain is triggered by the acidic pH of the endosome lumen. An essential step of the conformational change is the formation of an extended coiled-coil motif exposing the hydrophobic fusion peptide toward the target membrane. The structures of the neutral-pH, non-fusion active conformation of the HA ectodomain and of a fragment of the ectodomain containing the coiled-coil motif are known. However, it is not known by which mechanism protonation triggers the conformational change of the stable neutral-pH conformation of the ectodomain. Here, recent studies on the stability of the HA ectodomain at neutral pH, the energetics of the conformational change toward the fusion-active state and of the unfolding of the HA ectodomain are summarised. A model for the early steps of the conformational change of the HA ectodomain is presented. The model implicates that protonation leads to a partial dissociation of the distal domains of the HA monomers that is driven by electrostatic repulsion. The opening of the ectodomain enables water to enter the ectodomain. The interaction of water with respective sequences originally shielded from contact with water drives the formation of the coiled-coil structure.
authors.affiliation: Department of Chemistry, National Sun Yat-sen University, 80424, Kaohsiung, Taiwan, ROC.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Rachakonda P
authors.initials: RP
authors.lastname: Sivaramakrishna
authors.forename: Kai
authors.initials: K
authors.lastname: Ludwig
authors.forename: Thomas
authors.initials: T
authors.lastname: Korte
authors.forename: Christoph
authors.initials: C
authors.lastname: Böttcher
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
mesh_terms: D011992:Endosomes / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000821:virology; D007700:Kinetics; D008561:Membrane Fusion; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus