The transmembrane domain of influenza A M2 protein forms amantadine-sensitive proton channels in planar lipid bilayers.
In a direct test of the hypothesis that the M2 coat protein of influenza A can function as a proton translocator, we incorporated a synthetic peptide containing its putative transmembrane domain into voltage-clamped planar lipid bilayers. We observed single proton-selective ion channels with a conductance of approximately 10 pS at a pH of 2.3, consistent with the association of several monomers around a central water-filled pore. The channels were reversibly blocked by the anti-influenza drug amantadine. These experiments imply a central role for M2 protein in virus replication and assembly and may explain the mechanism of action of amantadine. Analogous proteins may have a similar function in other viruses, and these may be susceptible to similar antiviral agents.
Duff
K C
KC
Department of Biochemistry, University of Edinburgh, U.K.
Ashley
R H
RH
D000547:Amantadine / Q000494:pharmacology*; D004553:Electric Conductivity; D009980:Influenza A virus / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism*; D011522:Protons; D014763:Viral Matrix Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
D000547:Amantadine; D007473:Ion Channels; D008051:Lipid Bilayers; D011522:Protons; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins