4G7V

Crystal structure of voltage sensing domain of Ci-VSP with fragment antibody (R217E, 2.5 A)

Summary for 4G7V

• Entry DOI: 10.2210/pdb4g7v/pdb
• Related: 4G7Y 4G80
• Descriptor: fragment antibody heavy chain, fragment antibody light chain, Voltage-sensor containing phosphatase, ... (7 entities in total)
• Functional Keywords: membrane protein, alpha helix, fragment antibody, voltage sensing domain, sensing voltage
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 68206.71

Authors

Li, Q. (deposition date: 2012-07-20, release date: 2014-02-05, Last modification date: 2024-11-06)

Primary citation

Li, Q.,Wanderling, S.,Paduch, M.,Medovoy, D.,Singharoy, A.,McGreevy, R.,Villalba-Galea, C.A.,Hulse, R.E.,Roux, B.,Schulten, K.,Kossiakoff, A.,Perozo, E.
Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain.
Nat. Struct. Mol. Biol., 21:244-252, 2014

PubMed 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.

PubMed: 24487958
DOI: 10.1038/nsmb.2768

Experimental method

X-RAY DIFFRACTION (2.5 Å)