The sliding-helix voltage sensor: mesoscale views of a robust structure-function relationship.
The voltage sensor (VS) domain of voltage-gated ion channels underlies the electrical excitability of living cells. We simulate a mesoscale model of the VS domain to determine the functional consequences of some of its physical elements. Our mesoscale model is based on VS charges, linear dielectrics, and whole-body motion, applied to an S4 "sliding helix." The electrostatics under voltage-clamped boundary conditions are solved consistently using a boundary-element method. Based on electrostatic configurational energy, statistical-mechanical expectations of the experimentally observable relation between displaced charge and membrane voltage are predicted. Consequences of the model are investigated for variations of S4 configuration (α- and 3(10)-helical), countercharge alignment with S4 charges, protein polarizability, geometry of the gating canal, screening of S4 charges by the baths, and fixed charges located at the bath interfaces. The sliding-helix VS domain has an inherent electrostatic stability in the explored parameter space: countercharges present in the region of weak dielectric always retain an equivalent S4 charge in that region but allow sliding movements displacing 3-4 e                         (0). That movement is sensitive to small energy variations (<2 kT) along the path dependent on a number of electrostatic parameters tested in our simulations. These simulations show how the slope of the relation between displaced charge and voltage could be tuned in a channel.
Department of Physiology and Biophysics, University of Miami Computational Biophysics, German Research School for Simulation Sciences, Jülich, Germany. peyser.alex@gmail.com
Alexander
A
Peyser
Wolfgang
W
Nonner
D020816:Amino Acid Motifs; D015640:Ion Channel Gating; D056004:Molecular Dynamics Simulation; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000502:physiology; D017434:Protein Structure, Tertiary
D024642:Potassium Channels, Voltage-Gated