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J. Biol. Chem., Vol. 277, Issue 42, 39880-39886, October 18, 2002
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From the 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 Trp41 blocking the pore of
the M2 channel when pHout is high and with this
side chain leaving the pore when pHout is low. Thus,
the Trp41 side chain acts as the gate that opens and closes
the pore.
The Gate of the Influenza Virus M2 Proton Channel Is
Formed by a Single Tryptophan Residue*
,,
, and**
Department of Neurobiology and Physiology,
the § Department of Biochemistry, Molecular Biology, and
Cell Biology, and the ¶ Howard Hughes Medical Institute,
Northwestern University, Evanston, Illinois 60208-3500
*
This work was supported by Research Grants R37 AI-20201 (to
R. A. L.) and R01 AI-31882 (to L. H. P.) from NIAID, National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
An Investigator of the Howard Hughes Medical Institute.
**
To whom correspondence should be addressed: Dept. of Neurobiology
and Physiology, Hogan Hall, 2153 N. Campus Dr., Northwestern University, Evanston, IL 60208-3500. Tel.: 847-491-7915; Fax: 847-491-211; E-mail: larry-pinto@northwestern.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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