Structural and dynamic mechanisms for the function and inhibition of the M2 proton channel from influenza A virus.
The M2 proton channel from influenza A virus, a prototype for a class of viral ion channels known as viroporins, conducts protons along a chain of water molecules and ionizable sidechains, including His37. Recent studies highlight a delicate interplay between protein folding, proton binding, and proton conduction through the channel. Drugs inhibit proton conduction by binding to an aqueous cavity adjacent to M2's proton-selective filter, thereby blocking access of proton to the filter, and altering the energetic landscape of the channel and the energetics of proton-binding to His37.
Department of chemistry, University of Pennsylvania, 231 south, 34th st, Philadelphia, PA 19104, USA.
Jun
J
Wang
Jade Xiaoyan
JX
Qiu
Cinque
C
Soto
William F
WF
DeGrado
D000818:Animals; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry* / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism
D007473:Ion Channels; D014763:Viral Matrix Proteins
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