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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,
Electron microscopic analysis of KvAP voltage-dependent K+ channels in an open conformation.
2004,
Pubmed Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
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,
Activation and inactivation of homomeric KvLQT1 potassium channels.
1998,
Pubmed
,
Xenbase Pusch,
Increase of the single-channel conductance of KvLQT1 potassium channels induced by the association with minK.
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