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

132 Citations (Scopus)

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 - Jan 1 2014
Externally publishedYes

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Ciona intestinalis
Ion Channels
Spectrum Analysis
Membranes
Enzymes
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. / Li, Qufei; Wanderling, Sherry; Paduch, Marcin; Medovoy, David; Singharoy, Abhishek; Mcgreevy, Ryan; Villalba-Galea, Carlos A.; Hulse, Raymond E.; Roux, Benoît; Schulten, Klaus; Kossiakoff, Anthony; Perozo, Eduardo.

In: Nature Structural and Molecular Biology, Vol. 21, No. 3, 01.01.2014, p. 244-252.

Research output: Contribution to journalArticle

Li, Q, Wanderling, S, Paduch, M, Medovoy, D, Singharoy, A, Mcgreevy, R, Villalba-Galea, CA, Hulse, RE, 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, vol. 21, no. 3, pp. 244-252. https://doi.org/10.1038/nsmb.2768
Li, Qufei ; Wanderling, Sherry ; Paduch, Marcin ; Medovoy, David ; Singharoy, Abhishek ; Mcgreevy, Ryan ; Villalba-Galea, Carlos A. ; Hulse, Raymond E. ; Roux, Benoît ; Schulten, Klaus ; Kossiakoff, Anthony ; Perozo, Eduardo. / Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. In: Nature Structural and Molecular Biology. 2014 ; Vol. 21, No. 3. pp. 244-252.
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