title: Synchronized activation and refolding of influenza hemagglutinin in multimeric fusion machines.
abstract: At the time of fusion, membranes are packed with fusogenic proteins. Do adjacent individual proteins interact with each other in the plane of the membrane? Or does each of these proteins serve as an independent fusion machine? Here we report that the low pH-triggered transition between the initial and final conformations of a prototype fusogenic protein, influenza hemagglutinin (HA), involves a preserved interaction between individual HAs. Although the HAs of subtypes H3 and H2 show notably different degrees of activation, for both, the percentage of low pH-activated HA increased with higher surface density of HA, indicating positive cooperativity. We propose that a concerted activation of HAs, together with the resultant synchronized release of their conformational energy, is an example of a general strategy of coordination in biological design, crucial for the functioning of multiprotein fusion machines.
authors.affiliation: Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: I
authors.initials: I
authors.lastname: Markovic
authors.forename: E
authors.initials: E
authors.lastname: Leikina
authors.forename: M
authors.initials: M
authors.lastname: Zhukovsky
authors.forename: J
authors.initials: J
authors.lastname: Zimmerberg
authors.forename: L V
authors.initials: LV
authors.lastname: Chernomordik
mesh_terms: D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000502:physiology*; D008081:Liposomes / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D008954:Models, Biological; D017510:Protein Folding; D013820:Thermolysin / Q000494:pharmacology
chemical_list: D002087:Butyrates; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008081:Liposomes; D013820:Thermolysin; D004229:Dithiothreitol