The gate of the influenza virus M2 proton channel is formed by a single tryptophan residue.
The influenza virus M2 proton-selective ion channel is known to be essential for acidifying the interior of virions during virus uncoating in the lumen of endosomes. The M2 protein is a homotetramer that contains four 19-residue transmembrane (TM) domains. These TM domains are multifunctional, because they contain the channel pore and also anchor the protein in membranes. The M2 protein is gated by pH, and thus we have measured pH-gated currents, the accessibility of the pore to Cu2+, and the effect of a protein-modifying reagent for a series of TM domain mutant M2 proteins. The results indicate that gating of the M2 ion channel is governed by a single side chain at residue 41 of the TM domain and that this property is mediated by an indole moiety. Unlike many ion channels where the gate is formed by a whole segment of a protein, our data suggest a model of striking simplicity for the M2 ion channel protein, with the side chain of Trp(41) blocking the pore of the M2 channel when pH(out) is high and with this side chain leaving the pore when pH(out) is low. Thus, the Trp(41) side chain acts as the gate that opens and closes the pore.
Tang
Yajun
Y
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Zaitseva
Florina
F
Lamb
Robert A
RA
Pinto
Lawrence H
LH
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007700:Kinetics; D008564:Membrane Potentials; D008698:Mesylates / Q000737:chemistry; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014364:Tryptophan / Q000737:chemistry*; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism*; D014982:Xenopus laevis; D000086082:Viroporin Proteins
D003545:Cysteine; D018076:DNA, Complementary; D006639:Histidine; D007477:Ions; D008698:Mesylates; D014364:Tryptophan; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C074502:methanethiosulfonate