title: Studies on the structure of the influenza virus haemagglutinin at the pH of membrane fusion.
abstract: At the pH required to trigger the membrane fusion activity of the influenza virus haemagglutinin (HA) the soluble ectodomain of the molecule, BHA, which is released from virus by bromelain digestion, aggregates into rosettes. Analyses of soluble proteolytic fragments derived from the rosettes indicated that aggregation is mediated by association of the conserved hydrophobic amino-terminal region of BHA2, the smaller glycopolypeptide component of each BHA subunit. Further analyses of the structure of the soluble fragments and of HA in its low pH conformation by electron microscopy, spectroscopy and in crosslinking experiments showed that, although the membrane distal globular domains lose their trimer structure at the pH of fusion, the central fibrous stem of the molecule remains trimeric and assumes a more stable conformation. The increase in length of BHA2 at low pH observed microscopically appears to result from movement of the amino-terminal region to the membrane proximal end of the molecule and in virus incubated at low pH the amino terminus may insert into the virus membrane. The consequences of these possibilities for the mechanism of membrane fusion are discussed.
authors.affiliation: National Institute for Medical Research, Mill Hill, London, U.K.
authors.forename: R W
authors.initials: RW
authors.lastname: Ruigrok
authors.forename: A
authors.initials: A
authors.lastname: Aitken
authors.forename: L J
authors.initials: LJ
authors.lastname: Calder
authors.forename: S R
authors.initials: SR
authors.lastname: Martin
authors.forename: J J
authors.initials: JJ
authors.lastname: Skehel
authors.forename: S A
authors.initials: SA
authors.lastname: Wharton
authors.forename: W
authors.initials: W
authors.lastname: Weis
authors.forename: D C
authors.initials: DC
authors.lastname: Wiley
mesh_terms: D001963:Bromelains / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006389:Hemagglutinins, Viral / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000648:ultrastructure*; D046911:Macromolecular Substances; D008561:Membrane Fusion; D008854:Microscopy, Electron; D009975:Orthomyxoviridae / Q000502:physiology*
chemical_list: D006389:Hemagglutinins, Viral; D046911:Macromolecular Substances; D001963:Bromelains