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.
Biophys J
2011 Jan 19;1002:381-9. doi: 10.1016/j.bpj.2010.11.086.
Show Gene links
Show Anatomy links
Cholesterol sensitivity of KIR2.1 is controlled by a belt of residues around the cytosolic pore.
Rosenhouse-Dantsker A
,
Logothetis DE
,
Levitan I
.
???displayArticle.abstract???
Kir channels play an important role in setting the resting membrane potential and modulating membrane excitability. A common feature of several Kir channels is that they are regulated by cholesterol. Yet, the mechanism by which cholesterol affects channel function is unclear. We recently showed that the cholesterol sensitivity of Kir2 channels depends on several CD-loop residues. Here we show that this cytosolic loop is part of a regulatory site that also includes residues in the G-loop, the N-terminus, and the connecting segment between the C-terminus and the inner transmembrane helix. Together, these residues form a cytosolic belt that surrounds the pore of the channel close to its interface with the transmembrane domain, and modulate the cholesterol sensitivity of the channel. Furthermore, we show that residues in this cluster are correlated with residues located in the most flexible region of the G-loop, the major cytosolic gate of Kir2.1, implying that the importance of these residues extends beyond their effect on the channel's cholesterol sensitivity. We suggest that the residues of the cholesterol sensitivity belt are critical for channel gating.
Ambudkar,
Cellular domains that contribute to Ca2+ entry events.
2004, Pubmed
Ambudkar,
Cellular domains that contribute to Ca2+ entry events.
2004,
Pubmed
Bichet,
Merging functional studies with structures of inward-rectifier K(+) channels.
2003,
Pubmed
Bolotina,
Variations of membrane cholesterol alter the kinetics of Ca2(+)-dependent K+ channels and membrane fluidity in vascular smooth muscle cells.
1989,
Pubmed
Bowles,
Hypercholesterolemia inhibits L-type calcium current in coronary macro-, not microcirculation.
2004,
Pubmed
Clarke,
Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels.
2010,
Pubmed
Epand,
Cholesterol and the interaction of proteins with membrane domains.
2006,
Pubmed
Epshtein,
Identification of a C-terminus domain critical for the sensitivity of Kir2.1 to cholesterol.
2009,
Pubmed
Fang,
Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2.
2005,
Pubmed
Garneau,
Contribution of cytosolic cysteine residues to the gating properties of the Kir2.1 inward rectifier.
2003,
Pubmed
,
Xenbase
Gupta,
Conformational changes during the gating of a potassium channel revealed by structural mass spectrometry.
2010,
Pubmed
HUTTER,
Rectifying properties of heart muscle.
1960,
Pubmed
Haider,
Molecular dynamics simulations of inwardly rectifying (Kir) potassium channels: a comparative study.
2007,
Pubmed
He,
Identification of critical residues controlling G protein-gated inwardly rectifying K(+) channel activity through interactions with the beta gamma subunits of G proteins.
2002,
Pubmed
Heaps,
Hypercholesterolemia abolishes voltage-dependent K+ channel contribution to adenosine-mediated relaxation in porcine coronary arterioles.
2005,
Pubmed
Ho,
Molecular mechanism for sodium-dependent activation of G protein-gated K+ channels.
1999,
Pubmed
,
Xenbase
Ho,
Molecular determinants for sodium-dependent activation of G protein-gated K+ channels.
1999,
Pubmed
,
Xenbase
Inanobe,
Structural diversity in the cytoplasmic region of G protein-gated inward rectifier K+ channels.
2007,
Pubmed
Joy,
Detailed comparison of the protein-ligand docking efficiencies of GOLD, a commercial package and ArgusLab, a licensable freeware.
2006,
Pubmed
Kellner-Weibel,
Cytotoxic cholesterol is generated by the hydrolysis of cytoplasmic cholesteryl ester and transported to the plasma membrane.
1999,
Pubmed
Kruth,
Lipoprotein cholesterol and atherosclerosis.
2001,
Pubmed
Kubo,
International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels.
2005,
Pubmed
Kuo,
Two different conformational states of the KirBac3.1 potassium channel revealed by electron crystallography.
2005,
Pubmed
Kuo,
Crystal structure of the potassium channel KirBac1.1 in the closed state.
2003,
Pubmed
Levitan,
Cholesterol and Kir channels.
2009,
Pubmed
Levitan,
Cholesterol and ion channels.
2010,
Pubmed
Levitan,
Membrane cholesterol content modulates activation of volume-regulated anion current in bovine endothelial cells.
2000,
Pubmed
Li,
Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern.
1998,
Pubmed
Lockwich,
Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains.
2000,
Pubmed
Lopes,
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
2002,
Pubmed
,
Xenbase
Lundbaek,
Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol.
2004,
Pubmed
Lundbaek,
Membrane stiffness and channel function.
1996,
Pubmed
Maguy,
Involvement of lipid rafts and caveolae in cardiac ion channel function.
2006,
Pubmed
Martens,
Differential targeting of Shaker-like potassium channels to lipid rafts.
2000,
Pubmed
Martens,
Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae.
2001,
Pubmed
Nichols,
Inward rectifier potassium channels.
1997,
Pubmed
Nishida,
Crystal structure of a Kir3.1-prokaryotic Kir channel chimera.
2007,
Pubmed
Nishida,
Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
2002,
Pubmed
Olesen,
Haemodynamic shear stress activates a K+ current in vascular endothelial cells.
1988,
Pubmed
Pegan,
Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification.
2005,
Pubmed
,
Xenbase
Rohács,
Specificity of activation by phosphoinositides determines lipid regulation of Kir channels.
2003,
Pubmed
,
Xenbase
Romanenko,
Modulation of endothelial inward-rectifier K+ current by optical isomers of cholesterol.
2002,
Pubmed
Romanenko,
Sensitivity of volume-regulated anion current to cholesterol structural analogues.
2004,
Pubmed
Romanenko,
Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels.
2004,
Pubmed
Rosenhouse-Dantsker,
Molecular characteristics of phosphoinositide binding.
2007,
Pubmed
Rosenhouse-Dantsker,
A sodium-mediated structural switch that controls the sensitivity of Kir channels to PtdIns(4,5)P(2).
2008,
Pubmed
Rosenhouse-Dantsker,
Comparative analysis of cholesterol sensitivity of Kir channels: role of the CD loop.
2010,
Pubmed
,
Xenbase
Ross,
Atherosclerosis--an inflammatory disease.
1999,
Pubmed
Santiago,
Probing the effects of membrane cholesterol in the Torpedo californica acetylcholine receptor and the novel lipid-exposed mutation alpha C418W in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Singh,
Direct regulation of prokaryotic Kir channel by cholesterol.
2009,
Pubmed
Steinberg,
Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime.
2002,
Pubmed
Tai,
Ion-blocking sites of the Kir2.1 channel revealed by multiscale modeling.
2009,
Pubmed
Tao,
Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution.
2009,
Pubmed
,
Xenbase
Tikku,
Relationship between Kir2.1/Kir2.3 activity and their distributions between cholesterol-rich and cholesterol-poor membrane domains.
2007,
Pubmed
Toselli,
Caveolin-1 expression and membrane cholesterol content modulate N-type calcium channel activity in NG108-15 cells.
2005,
Pubmed
Wu,
The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte.
1995,
Pubmed
Xu,
Physical determinants of strong voltage sensitivity of K(+) channel block.
2009,
Pubmed
Yeagle,
Cholesterol and the cell membrane.
1985,
Pubmed
Yeagle,
Modulation of membrane function by cholesterol.
1991,
Pubmed
Zaritsky,
Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation.
2000,
Pubmed
Zhang,
Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions.
1999,
Pubmed
,
Xenbase
