Structure and function of the influenza A M2 proton channel.
The M2 protein of influenza A viruses forms a tetrameric pH-activated proton-selective channel that is targeted by the amantadine class of antiviral drugs. Its ion channel function has been extensively studied by electrophysiology and mutagenesis; however, the molecular mechanism of proton transport is still elusive, and the mechanism of inhibition by amantadine is controversial. We review the functional data on proton channel activity, molecular dynamics simulations of the proton conduction mechanism, and high-resolution structural and dynamical information of this membrane protein in lipid bilayers and lipid-mimetic detergents. These studies indicate that elucidation of the structural basis of M2 channel activity and inhibition requires thorough examination of the complex dynamics and conformational plasticity of the protein in different lipid bilayers and lipid-mimetic environments.
Cady
Sarah D
SD
Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA.
Luo
Wenbin
W
Hu
Fanghao
F
Hong
Mei
M
D000547:Amantadine / Q000737:chemistry; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D009980:Influenza A virus / Q000737:chemistry* / Q000502:physiology; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology; D008051:Lipid Bilayers / Q000737:chemistry; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011522:Protons; D013329:Structure-Activity Relationship; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology; D000086082:Viroporin Proteins
D000547:Amantadine; D007473:Ion Channels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D011522:Protons; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins