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

Publication Type:

Journal Article


Nat Struct Mol Biol, Volume 21, Issue 3, p.244-52 (2014)


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


<p>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. </p>

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