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Science 328 (5974): 67-73

Copyright © 2010 by the American Association for the Advancement of Science

A Gating Charge Transfer Center in Voltage Sensors

Xiao Tao,1 Alice Lee,1 Walrati Limapichat,2 Dennis A. Dougherty,2 Roderick MacKinnon1,*

Abstract: Voltage sensors regulate the conformations of voltage-dependent ion channels and enzymes. Their nearly switchlike response as a function of membrane voltage comes from the movement of positively charged amino acids, arginine or lysine, across the membrane field. We used mutations with natural and unnatural amino acids, electrophysiological recordings, and x-ray crystallography to identify a charge transfer center in voltage sensors that facilitates this movement. This center consists of a rigid cyclic "cap" and two negatively charged amino acids to interact with a positive charge. Specific mutations induce a preference for lysine relative to arginine. By placing lysine at specific locations, the voltage sensor can be stabilized in different conformations, which enables a dissection of voltage sensor movements and their relation to ion channel opening.

1 Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
2 Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.

* To whom correspondence should be addressed. E-mail: mackinn{at}rockefeller.edu

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