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
2014 May 13;11119:E1950-9. doi: 10.1073/pnas.1406161111.
Show Gene links
Show Anatomy links
Moving gating charges through the gating pore in a Kv channel voltage sensor.
Lacroix JJ, Hyde HC, Campos FV, Bezanilla F.
???displayArticle.abstract???
Voltage sensor domains (VSDs) regulate ion channels and enzymes by transporting electrically charged residues across a hydrophobic VSD constriction called the gating pore or hydrophobic plug. How the gating pore controls the gating charge movement presently remains debated. Here, using saturation mutagenesis and detailed analysis of gating currents from gating pore mutations in the Shaker Kv channel, we identified statistically highly significant correlations between VSD function and physicochemical properties of gating pore residues. A necessary small residue at position S240 in S1 creates a "steric gap" that enables an intracellular access pathway for the transport of the S4 Arg residues. In addition, the stabilization of the depolarized VSD conformation, a hallmark for most Kv channels, requires large side chains at positions F290 in S2 and F244 in S1 acting as "molecular clamps," and a hydrophobic side chain at position I237 in S1 acting as a local intracellular hydrophobic barrier. Finally, both size and hydrophobicity of I287 are important to control the main VSD energy barrier underlying transitions between resting and active states. Taken together, our study emphasizes the contribution of several gating pore residues to catalyze the gating charge transfer. This work paves the way toward understanding physicochemical principles underlying conformational dynamics in voltage sensors.
Adelman,
Episodic ataxia results from voltage-dependent potassium channels with altered functions.
1995, Pubmed,
Xenbase
Adelman,
Episodic ataxia results from voltage-dependent potassium channels with altered functions.
1995,
Pubmed
,
Xenbase Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996,
Pubmed
,
Xenbase Ahern,
Focused electric field across the voltage sensor of potassium channels.
2005,
Pubmed
,
Xenbase Asamoah,
A fluorometric approach to local electric field measurements in a voltage-gated ion channel.
2003,
Pubmed Batulan,
An intersubunit interaction between S4-S5 linker and S6 is responsible for the slow off-gating component in Shaker K+ channels.
2010,
Pubmed Ben-Chaim,
Movement of 'gating charge' is coupled to ligand binding in a G-protein-coupled receptor.
2006,
Pubmed
,
Xenbase Bezanilla,
The gating charge should not be estimated by fitting a two-state model to a Q-V curve.
2013,
Pubmed Biel,
Hyperpolarization-activated cation channels: from genes to function.
2009,
Pubmed Browne,
Identification of two new KCNA1 mutations in episodic ataxia/myokymia families.
1995,
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 Chamberlin,
Hydrophobic plug functions as a gate in voltage-gated proton channels.
2014,
Pubmed Chanda,
A common pathway for charge transport through voltage-sensing domains.
2008,
Pubmed Chen,
Structure of the full-length Shaker potassium channel Kv1.2 by normal-mode-based X-ray crystallographic refinement.
2010,
Pubmed Delemotte,
Intermediate states of the Kv1.2 voltage sensor from atomistic molecular dynamics simulations.
2011,
Pubmed Donald,
Salt bridges: geometrically specific, designable interactions.
2011,
Pubmed El Chemaly,
Do Hv1 proton channels regulate the ionic and redox homeostasis of phagosomes?
2012,
Pubmed Fujiwara,
Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures.
2003,
Pubmed Hackos,
Scanning the intracellular S6 activation gate in the shaker K+ channel.
2002,
Pubmed
,
Xenbase Hessa,
Recognition of transmembrane helices by the endoplasmic reticulum translocon.
2005,
Pubmed HODGKIN,
A quantitative description of membrane current and its application to conduction and excitation in nerve.
1952,
Pubmed Imbrici,
Episodic ataxia type 1 mutations in the KCNA1 gene impair the fast inactivation properties of the human potassium channels Kv1.4-1.1/Kvbeta1.1 and Kv1.4-1.1/Kvbeta1.2.
2006,
Pubmed
,
Xenbase Islas,
Electrostatics and the gating pore of Shaker potassium channels.
2001,
Pubmed
,
Xenbase Jacobson,
Calcium-activated and voltage-gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses.
2010,
Pubmed Jensen,
Mechanism of voltage gating in potassium channels.
2012,
Pubmed Khalili-Araghi,
Calculation of the gating charge for the Kv1.2 voltage-activated potassium channel.
2010,
Pubmed Kwong,
Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.
2012,
Pubmed Kyte,
A simple method for displaying the hydropathic character of a protein.
1982,
Pubmed Lacroix,
Intermediate state trapping of a voltage sensor.
2012,
Pubmed
,
Xenbase Lacroix,
Properties of deactivation gating currents in Shaker channels.
2011,
Pubmed Lacroix,
Control of a final gating charge transition by a hydrophobic residue in the S2 segment of a K+ channel voltage sensor.
2011,
Pubmed
,
Xenbase Lacroix,
Molecular bases for the asynchronous activation of sodium and potassium channels required for nerve impulse generation.
2013,
Pubmed
,
Xenbase Lacroix,
Tuning the voltage-sensor motion with a single residue.
2012,
Pubmed Ledwell,
Mutations in the S4 region isolate the final voltage-dependent cooperative step in potassium channel activation.
1999,
Pubmed
,
Xenbase Lin,
R1 in the Shaker S4 occupies the gating charge transfer center in the resting state.
2011,
Pubmed
,
Xenbase Li-Smerin,
A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.
2000,
Pubmed
,
Xenbase Li-Smerin,
alpha-helical structural elements within the voltage-sensing domains of a K(+) channel.
2000,
Pubmed
,
Xenbase Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed Mathur,
Ile-177 and Ser-180 in the S1 segment are critically important in Kv1.1 channel function.
1999,
Pubmed
,
Xenbase Miller,
Interior and surface of monomeric proteins.
1987,
Pubmed Murata,
Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
2005,
Pubmed
,
Xenbase Muroi,
Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel.
2010,
Pubmed Musset,
Aspartate 112 is the selectivity filter of the human voltage-gated proton channel.
2011,
Pubmed Papazian,
Alteration of voltage-dependence of Shaker potassium channel by mutations in the S4 sequence.
1991,
Pubmed
,
Xenbase Paulussen,
Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients.
2004,
Pubmed Perozo,
Gating currents from a nonconducting mutant reveal open-closed conformations in Shaker K+ channels.
1993,
Pubmed Petitprez,
A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia.
2008,
Pubmed Pless,
Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels.
2013,
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 Sasaki,
A voltage sensor-domain protein is a voltage-gated proton channel.
2006,
Pubmed Schwaiger,
The conserved phenylalanine in the K+ channel voltage-sensor domain creates a barrier with unidirectional effects.
2013,
Pubmed
,
Xenbase Seoh,
Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
1996,
Pubmed
,
Xenbase Singh,
A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome.
2009,
Pubmed Soler-Llavina,
Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.
2006,
Pubmed
,
Xenbase Starace,
Histidine scanning mutagenesis of basic residues of the S4 segment of the shaker k+ channel.
2001,
Pubmed
,
Xenbase Starace,
A proton pore in a potassium channel voltage sensor reveals a focused electric field.
2004,
Pubmed Stefani,
Cut-open oocyte voltage-clamp technique.
1998,
Pubmed
,
Xenbase Swartz,
Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.
1997,
Pubmed 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 Vargas,
An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations.
2012,
Pubmed Wimley,
Experimentally determined hydrophobicity scale for proteins at membrane interfaces.
1996,
Pubmed Yang,
How does the W434F mutation block current in Shaker potassium channels?
1997,
Pubmed
,
Xenbase Yang,
Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes.
2002,
Pubmed Yifrach,
Energetics of pore opening in a voltage-gated K(+) channel.
2002,
Pubmed
,
Xenbase Zhu,
Proton channel HVCN1 is required for effector functions of mouse eosinophils.
2013,
Pubmed Zhu,
Characterization of the Kv1.1 I262T and S342I mutations associated with episodic ataxia 1 with distinct phenotypes.
2012,
Pubmed
