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Biophys J
2006 Mar 15;906:2235-44. doi: 10.1529/biophysj.105.067165.
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Differential roles of S6 domain hinges in the gating of KCNQ potassium channels.
Seebohm G
,
Strutz-Seebohm N
,
Ureche ON
,
Baltaev R
,
Lampert A
,
Kornichuk G
,
Kamiya K
,
Wuttke TV
,
Lerche H
,
Sanguinetti MC
,
Lang F
.
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Voltage-gated K+ channel activation is proposed to result from simultaneous bending of all S6 segments away from the central axis, enlarging the aperture of the pore sufficiently to permit diffusion of K+ into the water-filled central cavity. The hinge position for the bending motion of each S6 segment is proposed to be a Gly residue and/or a Pro-Val-Pro motif in Kv1-Kv4 channels. The KCNQ1 (Kv7.1) channel has Ala-336 in the Gly-hinge position and Pro-Ala-Gly. Here we show that mutation of Ala-336 to Gly in KCNQ1 increased current amplitude and shifted the voltage dependence of activation to more negative potentials, consistent with facilitation of hinge activity that favors the open state. In contrast, mutation of Ala-336 to Cys or Thr shifted the voltage dependence of activation to more positive potentials and reduced current amplitude. Mutation of the putative Gly hinge to Ala in KCNQ2 (Kv7.2) abolished channel function. Mutation-dependent changes in current amplitude, but not kinetics, were found in heteromeric KCNQ1/KCNE1 channels. Mutation of the Pro or Gly of the Pro-Ala-Gly motif to Ala abolished KCNQ1 function and introduction of Gly in front of the Ala-mutations partially recovered channel function, suggesting that flexibility at the PAG is important for channel activation.
Ahern,
Specificity of charge-carrying residues in the voltage sensor of potassium channels.
2004, Pubmed
Ahern,
Specificity of charge-carrying residues in the voltage sensor of potassium channels.
2004,
Pubmed
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase
Chung,
Modeling diverse range of potassium channels with Brownian dynamics.
2002,
Pubmed
Cordes,
Proline-induced distortions of transmembrane helices.
2002,
Pubmed
Cuello,
Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer.
2004,
Pubmed
del Camino,
Blocker protection in the pore of a voltage-gated K+ channel and its structural implications.
2000,
Pubmed
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Durell,
Models of the structure and voltage-gating mechanism of the shaker K+ channel.
2004,
Pubmed
Heinemann,
Nonstationary noise analysis and application to patch clamp recordings.
1992,
Pubmed
Holmgren,
The activation gate of a voltage-gated K+ channel can be trapped in the open state by an intersubunit metal bridge.
1998,
Pubmed
Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed
Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
Pubmed
Jiang,
Electron microscopic analysis of KvAP voltage-dependent K+ channels in an open conformation.
2004,
Pubmed
Jin,
The (beta)gamma subunits of G proteins gate a K(+) channel by pivoted bending of a transmembrane segment.
2002,
Pubmed
,
Xenbase
Labro,
Gating of shaker-type channels requires the flexibility of S6 caused by prolines.
2003,
Pubmed
Lainé,
Critical assessment of a proposed model of Shaker.
2004,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
Magidovich,
Conserved gating hinge in ligand- and voltage-dependent K+ channels.
2004,
Pubmed
,
Xenbase
Melman,
KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity.
2004,
Pubmed
Mitcheson,
A structural basis for drug-induced long QT syndrome.
2000,
Pubmed
,
Xenbase
Pusch,
Increase of the single-channel conductance of KvLQT1 potassium channels induced by the association with minK.
1998,
Pubmed
,
Xenbase
Pusch,
Activation and inactivation of homomeric KvLQT1 potassium channels.
1998,
Pubmed
,
Xenbase
Sadja,
Coupling Gbetagamma-dependent activation to channel opening via pore elements in inwardly rectifying potassium channels.
2001,
Pubmed
,
Xenbase
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Seebohm,
Identification of specific pore residues mediating KCNQ1 inactivation. A novel mechanism for long QT syndrome.
2001,
Pubmed
,
Xenbase
Seebohm,
Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels.
2003,
Pubmed
,
Xenbase
Seebohm,
Molecular determinants of KCNQ1 channel block by a benzodiazepine.
2003,
Pubmed
,
Xenbase
Sesti,
Single-channel characteristics of wild-type IKs channels and channels formed with two minK mutants that cause long QT syndrome.
1998,
Pubmed
,
Xenbase
Shealy,
Sequence-function analysis of the K+-selective family of ion channels using a comprehensive alignment and the KcsA channel structure.
2003,
Pubmed
Shrivastava,
A model of voltage gating developed using the KvAP channel crystal structure.
2004,
Pubmed
Starace,
A proton pore in a potassium channel voltage sensor reveals a focused electric field.
2004,
Pubmed
Stühmer,
Electrophysiological recording from Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Treptow,
Coupled motions between pore and voltage-sensor domains: a model for Shaker B, a voltage-gated potassium channel.
2004,
Pubmed
Tristani-Firouzi,
Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits.
1998,
Pubmed
,
Xenbase
Webster,
Intracellular gate opening in Shaker K+ channels defined by high-affinity metal bridges.
2004,
Pubmed
Yang,
Single-channel properties of IKs potassium channels.
1998,
Pubmed
,
Xenbase
Yifrach,
Energetics of pore opening in a voltage-gated K(+) channel.
2002,
Pubmed
,
Xenbase
Zhao,
A gating hinge in Na+ channels; a molecular switch for electrical signaling.
2004,
Pubmed
