title: A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity.
abstract: The M2 protein from influenza A virus forms proton-selective channels that are essential to viral function and are the target of the drug amantadine. Cys scanning was used to generate a series of mutants with successive substitutions in the transmembrane segment of the protein, and the mutants were expressed in Xenopus laevis oocytes. The effect of the mutations on reversal potential, ion currents, and amantadine resistance were measured. Fourier analysis revealed a periodicity consistent with a four-stranded coiled coil or helical bundle. A three-dimensional model of this structure suggests a possible mechanism for the proton selectivity of the M2 channel of influenza virus.
authors.affiliation: Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208-3500, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Pinto
authors.forename: G R
authors.initials: GR
authors.lastname: Dieckmann
authors.forename: C S
authors.initials: CS
authors.lastname: Gandhi
authors.forename: C G
authors.initials: CG
authors.lastname: Papworth
authors.forename: J
authors.initials: J
authors.lastname: Braman
authors.forename: M A
authors.initials: MA
authors.lastname: Shaughnessy
authors.forename: J D
authors.initials: JD
authors.lastname: Lear
authors.forename: R A
authors.initials: RA
authors.lastname: Lamb
authors.forename: W F
authors.initials: WF
authors.lastname: DeGrado
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D003198:Computer Simulation; D003545:Cysteine; D004553:Electric Conductivity; D005260:Female; D009980:Influenza A virus / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000502:physiology*; D014982:Xenopus laevis; D000086082:Viroporin Proteins
chemical_list: D003545:Cysteine; D007473:Ion Channels; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins