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Voltage Sensor of Kv1.2: Structural Basis of Electromechanical Coupling
Stephen B. Long,
Ernest B. Campbell,
Roderick MacKinnon*
Abstract:
Voltage-dependent ion channels contain voltage sensors thatallow them to switch between nonconductive and conductive statesover the narrow range of a few hundredths of a volt. We investigatedthe mechanism by which these channels sense cell membrane voltageby determining the x-ray crystal structure of a mammalian Shakerfamily potassium ion (K+) channel. The voltage-dependent K+channel Kv1.2 grew three-dimensional crystals, with an internalarrangement that left the voltage sensors in an apparently nativeconformation, allowing us to reach three important conclusions.First, the voltage sensors are essentially independent domainsinside the membrane. Second, they perform mechanical work onthe pore through the S4-S5 linker helices, which are positionedto constrict or dilate the S6 inner helices of the pore. Third,in the open conformation, two of the four conserved Arg residueson S4 are on a lipid-facing surface and two are buried in thevoltage sensor. The structure offers a simple picture of howmembrane voltage influences the open probability of the channel.
Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
* To whom correspondence should be addressed. E-mail: mackinn{at}rockefeller.edu
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