@article{12ce0510b56b4dfea19c05c59f8678b0,
title = "Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain",
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-{\AA} 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.",
author = "Qufei Li and Sherry Wanderling and Marcin Paduch and David Medovoy and Abhishek Singharoy and Ryan Mcgreevy and Villalba-Galea, {Carlos A.} and Hulse, {Raymond E.} and Beno{\^i}t Roux and Klaus Schulten and Anthony Kossiakoff and Eduardo Perozo",
note = "Funding Information: We are thankful to K. Rajashankar and the staff at the NE-CAT 24-ID beamline as well as to R. Sanishvili and the staff at the GM/CA 23-ID beamline in the Advanced Photon Source, Argonne National Laboratory. We thank the Perozo, Bezanilla and Roux laboratories for illuminating discussions and invaluable experimental advice and A. Koide and S. Koide (University of Chicago) for the antibody library. We are grateful to E.J. Adams, R. Keenan, P. Rice and X. Yang for helpful crystallographic advice. The US National Resource provided Anton computer time for Biomedical Supercomputing and the Pittsburgh Supercomputing Center through grants RC2GM093307 and PSCA13070P (to E.P.) from the US National Institutes of Health. This work was supported in part by US National Institutes of Health grants R01-GM57846 (to E.P.), U54-GM74946 (to E.P.), R01-GM062342 (to B.R.), 9P41-GM104601 (to K.S.), U54-GM087519 (to K.S.) and 5R01-GM098243-02 (to K.S.) and a Beckman Postdoctoral Fellowship to A.S.",
year = "2014",
month = mar,
doi = "10.1038/nsmb.2768",
language = "English (US)",
volume = "21",
pages = "244--252",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Research",
number = "3",
}