Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain
| Autor: | Qufei Li, Eduardo Perozo, Klaus Schulten, David Medovoy, Sherry Wanderling, Raymond E. Hulse, Anthony A. Kossiakoff, Carlos A. Villalba-Galea, Abhishek Singharoy, Ryan McGreevy, Benoît Roux, Marcin Paduch |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Molecular Sequence Data Static Electricity Gating Crystallography X-Ray Article Xenopus laevis Protein structure Structural Biology Electric field Static electricity Escherichia coli Animals Humans Amino Acid Sequence Molecular Biology Ion channel Physics Sequence Homology Amino Acid Cell Membrane Electron Spin Resonance Spectroscopy Transmembrane protein Ciona intestinalis Protein Structure Tertiary Electrophysiology Crystallography Transduction (biophysics) Helix Oocytes Biophysics |
| Zdroj: | Nature Structural & Molecular Biology. 21:244-252 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb.2768 |
| Popis: | The transduction of transmembrane electric fields into protein motion plays an essential role in the generation and propagation of cellular signals. Voltage-sensing domains (VSD) carry out these functions through reorientations of S4 helix with discrete gating charges. Here, crystal structures of the VSD from Ci-VSP were determined in both, active (Up) and resting (Down) conformations. The S4 undergoes a ~5 Å displacement along its main axis accompanied by a ~60o rotation, consistent with the helix-screw gating mechanism. This movement is stabilized by a change in countercharge partners in helices S1 and S3, generating 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 cellular activities. |
| Databáze: | OpenAIRE |
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