title: Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes.
abstract: Successful uncoating of the influenza B virus in endosomes is predicted to require acidification of the interior of the virus particle. We report that a virion component, the BM2 integral membrane protein, when expressed in Xenopus oocytes or in mammalian cells, causes acidification of the cells and possesses ion channel activity consistent with proton conduction. Furthermore, coexpression of BM2 with hemagglutinin (HA) glycoprotein prevents HA from adopting its low-pH-induced conformation during transport to the cell surface, and overexpression of BM2 causes a delay in intracellular transport in the exocytic pathway and causes morphological changes in the Golgi. These data are consistent with BM2 equilibrating the pH gradient between the Golgi and the cytoplasm. The transmembrane domain of BM2 protein and the influenza A virus A/M2 ion channel protein both contain the motif HXXXW, and, for both proteins, the His and Trp residues are important for channel function.
authors.affiliation: Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jorgen A
authors.initials: JA
authors.lastname: Mould
authors.forename: Reay G
authors.initials: RG
authors.lastname: Paterson
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohigashi
authors.forename: Padma
authors.initials: P
authors.lastname: Venkataraman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lamb
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Pinto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009981:Influenza B virus / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D009154:Mutation; D009865:Oocytes / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
chemical_list: D006389:Hemagglutinins, Viral; D007473:Ion Channels; D011522:Protons; D014763:Viral Matrix Proteins