title: Solution structure and functional analysis of the influenza B proton channel.
abstract: Influenza B virus contains an integral membrane protein, BM2, that oligomerizes in the viral membrane to form a pH-activated proton channel. Here we report the solution structures of both the membrane-embedded channel domain and the cytoplasmic domain of BM2. The channel domain assumes a left-handed coiled-coil tetramer formation with a helical packing angle of -37 degrees to form a polar pore in the membrane for conducting ions. Mutagenesis and proton flux experiments identified residues involved in proton relay and suggest a mechanism of proton conductance. The cytoplasmic domain of BM2 also forms a coiled-coil tetramer. It has a bipolar charge distribution, in which a negatively charged region interacts specifically with the M1 matrix protein that is involved in packaging the genome in the virion. This interaction suggests BM2 also recruits matrix proteins to the cell surface during virus budding, making BM2 an unusual membrane protein with the dual roles of conducting ions and recruiting proteins to the membrane.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Rafal M
authors.initials: RM
authors.lastname: Pielak
authors.forename: Mark A
authors.initials: MA
authors.lastname: McClintock
authors.forename: James J
authors.initials: JJ
authors.lastname: Chou
mesh_terms: D009981:Influenza B virus / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011522:Protons; D014763:Viral Matrix Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C064964:BM2 polypeptide, influenza B virus; C545845:M1 matrix protein, influenza B virus; D011522:Protons; D014763:Viral Matrix Proteins; D014764:Viral Proteins