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Published Online July 7, 2005
Science DOI: 10.1126/science.1116270

Research Articles

Submitted on June 17, 2005
Accepted on July 5, 2005

Voltage Sensor of Kv1.2: Structural Basis of Electromechanical Coupling

Stephen B. Long 1, Ernest B. Campbell 1, Roderick MacKinnon 1*

1 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.
Roderick MacKinnon , E-mail: mackinn{at}rockefeller.edu

Voltage-dependent ion channels contain voltage sensors that allow them to switch between nonconductive and conductive states over the narrow range of a few hundredths of a volt. We investigated the mechanism by which these channels sense cell membrane voltage by determining the X-ray crystal structure of a mammalian Shaker family K+ channel. The voltage-dependent K+ channel Kv1.2 grew 3-dimensional crystals with an internal arrangement that leaves the voltage sensors in an apparently native conformation, allowing us to reach three important conclusions: first, the voltage sensors are essentially independent domains inside the membrane, second, they perform mechanical work on the pore through the S4-S5 linker helices which are positioned so as to constrict or dilate the S6 inner helices of the pore, and third, of the four conserved Arg residues on S4, in the open conformation two are on a lipid facing surface and two are buried in the voltage sensor. The structure offers a simple picture of how membrane voltage influences channel open probability.


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