Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2012 May 29;10922:8552-7. doi: 10.1073/pnas.1116938109.
Show Gene links
Show Anatomy links
Tracking a complete voltage-sensor cycle with metal-ion bridges.
Henrion U, Renhorn J, Börjesson SI, Nelson EM, Schwaiger CS, Bjelkmar P, Wallner B, Lindahl E, Elinder F.
???displayArticle.abstract???
Voltage-gated ion channels open and close in response to changes in membrane potential, thereby enabling electrical signaling in excitable cells. The voltage sensitivity is conferred through four voltage-sensor domains (VSDs) where positively charged residues in the fourth transmembrane segment (S4) sense the potential. While an open state is known from the Kv1.2/2.1 X-ray structure, the conformational changes underlying voltage sensing have not been resolved. We present 20 additional interactions in one open and four different closed conformations based on metal-ion bridges between all four segments of the VSD in the voltage-gated Shaker K channel. A subset of the experimental constraints was used to generate Rosetta models of the conformations that were subjected to molecular simulation and tested against the remaining constraints. This achieves a detailed model of intermediate conformations during VSD gating. The results provide molecular insight into the transition, suggesting that S4 slides at least 12 Å along its axis to open the channel with a 3(10) helix region present that moves in sequence in S4 in order to occupy the same position in space opposite F290 from open through the three first closed states.
Berger,
Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature.
1997, Pubmed
Berger,
Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature.
1997,
Pubmed Börjesson,
Structure, function, and modification of the voltage sensor in voltage-gated ion channels.
2008,
Pubmed Börjesson,
Electrostatic tuning of cellular excitability.
2010,
Pubmed
,
Xenbase Börjesson,
An electrostatic potassium channel opener targeting the final voltage sensor transition.
2011,
Pubmed
,
Xenbase Broomand,
Large-scale movement within the voltage-sensor paddle of a potassium channel-support for a helical-screw motion.
2008,
Pubmed
,
Xenbase Bussi,
Canonical sampling through velocity rescaling.
2007,
Pubmed Campos,
Two atomic constraints unambiguously position the S4 segment relative to S1 and S2 segments in the closed state of Shaker K channel.
2007,
Pubmed
,
Xenbase Careaga,
Thermal motions of surface alpha-helices in the D-galactose chemosensory receptor. Detection by disulfide trapping.
1992,
Pubmed Catterall,
Ion channel voltage sensors: structure, function, and pathophysiology.
2010,
Pubmed Catterall,
Voltage-gated ion channels and gating modifier toxins.
2007,
Pubmed COLE,
Potassium ion current in the squid giant axon: dynamic characteristic.
1960,
Pubmed DeCaen,
Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation.
2008,
Pubmed DeCaen,
Sequential formation of ion pairs during activation of a sodium channel voltage sensor.
2009,
Pubmed Delemotte,
Intermediate states of the Kv1.2 voltage sensor from atomistic molecular dynamics simulations.
2011,
Pubmed Domene,
Voltage-sensor cycle fully described.
2012,
Pubmed Hess,
GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.
2008,
Pubmed Hessa,
Membrane insertion of a potassium-channel voltage sensor.
2005,
Pubmed Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase Kamb,
Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity.
1988,
Pubmed Keynes,
Modelling the activation, opening, inactivation and reopening of the voltage-gated sodium channel.
1998,
Pubmed Khalili-Araghi,
Molecular dynamics investigation of the ω-current in the Kv1.2 voltage sensor domains.
2012,
Pubmed Khalili-Araghi,
Calculation of the gating charge for the Kv1.2 voltage-activated potassium channel.
2010,
Pubmed Larsson,
A conserved glutamate is important for slow inactivation in K+ channels.
2000,
Pubmed
,
Xenbase Li,
Gating the pore of P2X receptor channels.
2008,
Pubmed Lin,
R1 in the Shaker S4 occupies the gating charge transfer center in the resting state.
2011,
Pubmed
,
Xenbase Lindorff-Larsen,
Improved side-chain torsion potentials for the Amber ff99SB protein force field.
2010,
Pubmed Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed Murata,
Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
2005,
Pubmed
,
Xenbase Papazian,
Electrostatic interactions of S4 voltage sensor in Shaker K+ channel.
1995,
Pubmed
,
Xenbase Pathak,
Closing in on the resting state of the Shaker K(+) channel.
2007,
Pubmed Payandeh,
The crystal structure of a voltage-gated sodium channel.
2011,
Pubmed Pless,
Contributions of counter-charge in a potassium channel voltage-sensor domain.
2011,
Pubmed
,
Xenbase Ramsey,
A voltage-gated proton-selective channel lacking the pore domain.
2006,
Pubmed Rulísek,
Coordination geometries of selected transition metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+) in metalloproteins.
1998,
Pubmed Sali,
Comparative protein modelling by satisfaction of spatial restraints.
1993,
Pubmed Sasaki,
A voltage sensor-domain protein is a voltage-gated proton channel.
2006,
Pubmed Schoppa,
Activation of Shaker potassium channels. III. An activation gating model for wild-type and V2 mutant channels.
1998,
Pubmed
,
Xenbase Schoppa,
The size of gating charge in wild-type and mutant Shaker potassium channels.
1992,
Pubmed Schow,
Down-state model of the voltage-sensing domain of a potassium channel.
2010,
Pubmed Schwaiger,
3₁₀-helix conformation facilitates the transition of a voltage sensor S4 segment toward the down state.
2011,
Pubmed Söding,
Protein homology detection by HMM-HMM comparison.
2005,
Pubmed Sokolov,
Gating pore current in an inherited ion channelopathy.
2007,
Pubmed
,
Xenbase Tao,
A gating charge transfer center in voltage sensors.
2010,
Pubmed
,
Xenbase Vargas,
In search of a consensus model of the resting state of a voltage-sensing domain.
2011,
Pubmed Villalba-Galea,
S4-based voltage sensors have three major conformations.
2008,
Pubmed Webster,
Intracellular gate opening in Shaker K+ channels defined by high-affinity metal bridges.
2004,
Pubmed Zagotta,
Shaker potassium channel gating. III: Evaluation of kinetic models for activation.
1994,
Pubmed
,
Xenbase
