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

Qufei Li, Sherry Wanderling, Marcin Paduch, David Medovoy, Abhishek Singharoy, Ryan Mcgreevy, Carlos A. Villalba-Galea, Raymond E. Hulse, Benoît Roux, Klaus Schulten, Anthony Kossiakoff, Eduardo Perozo

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

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 ∼60rotation. This movement is stabilized by an exchange in countercharge partners in helices S1 and S3 that generates an estimated net charge transfer of ∼1 e o. 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.

Original languageEnglish (US)
Pages (from-to)244-252
Number of pages9
JournalNature Structural and Molecular Biology
Volume21
Issue number3
DOIs
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Li, Q., Wanderling, S., Paduch, M., Medovoy, D., Singharoy, A., Mcgreevy, R., Villalba-Galea, C. A., Hulse, R. E., Roux, B., Schulten, K., Kossiakoff, A., & Perozo, E. (2014). Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. Nature Structural and Molecular Biology, 21(3), 244-252. https://doi.org/10.1038/nsmb.2768