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

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

Author information

1
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
2
Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
3
Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
4
1] Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA. [2] Institute of Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA.
5
1] Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. [2] Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

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 ~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.

PMID:
24487958
PMCID:
PMC4116111
DOI:
10.1038/nsmb.2768
[Indexed for MEDLINE]
Free PMC Article

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