Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain

Nat Struct Mol Biol. 2014 Mar;21(3):244-52. doi: 10.1038/nsmb.2768. Epub 2014 Feb 2.


The transduction of transmembrane electric fields into protein motion has an essential role in the generation and propagation of cellular signals. Voltage-sensing domains (VSDs) carry out these functions through reorientations of positive charges in the S4 helix. Here, we determined crystal structures of the Ciona intestinalis VSD (Ci-VSD) in putatively active and resting conformations. S4 undergoes an ~5-Å displacement along its main axis, accompanied by an ~60° rotation. This movement is stabilized by an exchange in countercharge partners in helices S1 and S3 that generates an estimated net charge transfer of ~1 eo. Gating charges move relative to a ''hydrophobic gasket' that electrically divides intra- and extracellular compartments. EPR spectroscopy confirms the limited nature of S4 movement in a membrane environment. These results provide an explicit mechanism for voltage sensing and set the basis for electromechanical coupling in voltage-dependent enzymes and ion channels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Membrane / metabolism
  • Ciona intestinalis / chemistry*
  • Crystallography, X-Ray
  • Electron Spin Resonance Spectroscopy
  • Electrophysiology
  • Escherichia coli / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Protein Structure, Tertiary*
  • Sequence Homology, Amino Acid
  • Static Electricity
  • Xenopus laevis / metabolism

Associated data

  • PDB/4G7V
  • PDB/4G7Y
  • PDB/4G80