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Proc Natl Acad Sci U S A
2010 Oct 26;10743:18700-5. doi: 10.1073/pnas.1010124107.
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Ion sensing in the RCK1 domain of BK channels.
Zhang G
,
Huang SY
,
Yang J
,
Shi J
,
Yang X
,
Moller A
,
Zou X
,
Cui J
.
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BK-type K(+) channels are activated by voltage and intracellular Ca(2+), which is important in modulating muscle contraction, neural transmission, and circadian pacemaker output. Previous studies suggest that the cytosolic domain of BK channels contains two different Ca(2+) binding sites, but the molecular composition of one of the sites is not completely known. Here we report, by systematic mutagenesis studies, the identification of E535 as part of this Ca(2+) binding site. This site is specific for binding to Ca(2+) but not Cd(2+). Experimental results and molecular modeling based on the X-ray crystallographic structures of the BK channel cytosolic domain suggest that the binding of Ca(2+) by the side chains of E535 and the previously identified D367 changes the conformation around the binding site and turns the side chain of M513 into a hydrophobic core, providing a basis to understand how Ca(2+) binding at this site opens the activation gate of the channel that is remotely located in the membrane.
Adelman,
Calcium-activated potassium channels expressed from cloned complementary DNAs.
1992,
Pubmed
,
Xenbase
Atkinson,
A component of calcium-activated potassium channels encoded by the Drosophila slo locus.
1991,
Pubmed
Bao,
Elimination of the BK(Ca) channel's high-affinity Ca(2+) sensitivity.
2002,
Pubmed
,
Xenbase
Bao,
Mapping the BKCa channel's "Ca2+ bowl": side-chains essential for Ca2+ sensing.
2004,
Pubmed
,
Xenbase
Braun,
Contribution of potential EF hand motifs to the calcium-dependent gating of a mouse brain large conductance, calcium-sensitive K(+) channel.
2001,
Pubmed
Brayden,
Regulation of arterial tone by activation of calcium-dependent potassium channels.
1992,
Pubmed
Butler,
mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels.
1993,
Pubmed
,
Xenbase
Cox,
Allosteric gating of a large conductance Ca-activated K+ channel.
1997,
Pubmed
,
Xenbase
Cui,
Allosteric linkage between voltage and Ca(2+)-dependent activation of BK-type mslo1 K(+) channels.
2000,
Pubmed
Cui,
Intrinsic voltage dependence and Ca2+ regulation of mslo large conductance Ca-activated K+ channels.
1997,
Pubmed
,
Xenbase
Cui,
Molecular mechanisms of BK channel activation.
2009,
Pubmed
Du,
Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.
2005,
Pubmed
,
Xenbase
Dudev,
Principles governing Mg, Ca, and Zn binding and selectivity in proteins.
2003,
Pubmed
Gu,
BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells.
2007,
Pubmed
Harding,
The architecture of metal coordination groups in proteins.
2004,
Pubmed
Horrigan,
Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels.
2002,
Pubmed
,
Xenbase
Huang,
An iterative knowledge-based scoring function for protein-protein recognition.
2008,
Pubmed
Jiang,
Crystal structure and mechanism of a calcium-gated potassium channel.
2002,
Pubmed
Lee,
BK channel activation: structural and functional insights.
2010,
Pubmed
Lee,
{beta} subunit-specific modulations of BK channel function by a mutation associated with epilepsy and dyskinesia.
2009,
Pubmed
,
Xenbase
Meredith,
BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output.
2006,
Pubmed
Moss,
An evolutionarily conserved binding site for serine proteinase inhibitors in large conductance calcium-activated potassium channels.
1996,
Pubmed
Oberhauser,
Activation by divalent cations of a Ca2+-activated K+ channel from skeletal muscle membrane.
1988,
Pubmed
Qian,
Intra- and intersubunit cooperativity in activation of BK channels by Ca2+.
2006,
Pubmed
,
Xenbase
Robitaille,
Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassium channels.
1992,
Pubmed
Schreiber,
A novel calcium-sensing domain in the BK channel.
1997,
Pubmed
,
Xenbase
Shen,
Tetraethylammonium block of Slowpoke calcium-activated potassium channels expressed in Xenopus oocytes: evidence for tetrameric channel formation.
1994,
Pubmed
,
Xenbase
Shi,
Mechanism of magnesium activation of calcium-activated potassium channels.
2002,
Pubmed
Soto,
Loop modeling: Sampling, filtering, and scoring.
2008,
Pubmed
Sweet,
Measurements of the BKCa channel's high-affinity Ca2+ binding constants: effects of membrane voltage.
2008,
Pubmed
Wang,
Structure of the BK potassium channel in a lipid membrane from electron cryomicroscopy.
2009,
Pubmed
Wu,
Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel.
2010,
Pubmed
Xia,
Multiple regulatory sites in large-conductance calcium-activated potassium channels.
2002,
Pubmed
Yang,
Mg2+ mediates interaction between the voltage sensor and cytosolic domain to activate BK channels.
2007,
Pubmed
Yang,
Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains.
2008,
Pubmed
Yang,
An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing.
2010,
Pubmed
,
Xenbase
Yuan,
Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution.
2010,
Pubmed
Zeng,
Divalent cation sensitivity of BK channel activation supports the existence of three distinct binding sites.
2005,
Pubmed
,
Xenbase
