The sliding-helix voltage sensor: Mesoscale views of a robust structure-function relationship

Alexander Peyser, Wolfgang Nonner

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The voltage sensor (VS) domain of voltagegated 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 (a- and 310-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 e0. 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.

Original languageEnglish (US)
Pages (from-to)705-721
Number of pages17
JournalEuropean Biophysics Journal
Volume41
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Computer simulation
  • Ion channels
  • Potassium channels
  • Voltage gated
  • Voltage sensor domain

ASJC Scopus subject areas

  • Biophysics

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