Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1
- Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065
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Contributed by Roderick MacKinnon, April 3, 2008 (received for review March 21, 2008)
Abstract
In voltage-gated Na+, K+, and Ca2+ channels, four voltage-sensor domains operate on a central pore domain in response to membrane voltage. In contrast, the voltage-gated proton channel (Hv) contains only a voltage-sensor domain, lacking a separate pore domain. The subunit stoichiometry and organization of Hv has been unknown. Here, we show that human Hv1 forms a dimer in the membrane and define regions that are close to the dimer interface by using cysteine cross-linking. Two dimeric interfaces appear to exist in Hv1, one mediated by S1 and the adjacent extracellular loop, and the other mediated by a putative intracellular coiled-coil domain. It may be significant that Hv1 uses for its dimer interface a surface that corresponds to the interface between the voltage sensor and pore in Kv channels.
Footnotes
- *To whom correspondence should be addressed. E-mail: mackinn{at}mail.rockefeller.edu
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Author contributions: S.-Y.L. and R.M. designed research; S.-Y.L. and J.A.L. performed research; S.-Y.L. and R.M. analyzed data; and S.-Y.L. and R.M. wrote the paper.
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The authors declare no conflict of interest.
- © 2008 by The National Academy of Sciences of the USA
