Members of the voltage-gated ion channel superfamily (VGIC) respond to voltage changes by opening and closing a central pore. The mechanics and the molecular details of coupling between voltage-sensing motions and pore gates remain poorly understood. Using two complementary methods, we have identified a common set of residues in the S4-S5 linker and S6 of domain III that are primarily involved in electromechanical coupling between voltage-sensor of domain III and the pore gates. This is first study to examine electromechanical coupling in ion channels that lack the symmetry of the voltage-gated potassium channels and shows that the site of coupling may be conserved in this superfamily.
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