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.
The I182 region of k(ir)6.2 is closely associated with ligand binding in K(ATP) channel inhibition by ATP.
Li L
,
Wang J
,
Drain P
.
???displayArticle.abstract???
The ATP-inhibited potassium (K(ATP)) channel is assembled from four inward rectifier potassium (K(ir)6.x) subunits and four sulfonylurea receptor (SURx) subunits. The inhibitory action of ATP is mediated by at least two distinct functional domains within the C-terminal cytoplasmic tail of K(ir)6.2. The G334D mutation of K(ir)6.2 virtually eliminates ATP-dependent gating with no effect on ligand-independent gating, suggesting a role in linkage of the site to the gate or in the ATP binding site, itself. The T171A mutation of K(ir)6.2 strongly disrupts both ATP-dependent and ligand-independent gating, suggesting a role for T171 in the gating step. A neighboring mutation, I182Q, virtually eliminates ATP inhibition, but its effect on ligand-independent gating remained unknown. We have now characterized both the K(i) values for inhibition by ATP and the ligand-independent gating kinetics of 15 substitutions at position 182. All substitutions decreased ATP-dependent inhibition gating as measured by the K(i), many profoundly so, yet had little or no effect on ligand-independent gating kinetics. Thus, substitutions at position 182 are unlikely to act by disrupting inhibition gate movement. Our results indicate an indispensable role for I182 in a step of the ATP binding mechanism, the linkage mechanism coupling the ATP binding site to the inhibition gate, or both.
Aguilar-Bryan,
Molecular biology of adenosine triphosphate-sensitive potassium channels.
1999, Pubmed
Aguilar-Bryan,
Molecular biology of adenosine triphosphate-sensitive potassium channels.
1999,
Pubmed
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995,
Pubmed
Alekseev,
Burst kinetics of co-expressed Kir6.2/SUR1 clones: comparison of recombinant with native ATP-sensitive K+ channel behavior.
1997,
Pubmed
Ashcroft,
Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells.
,
Pubmed
Babenko,
The N-terminus of KIR6.2 limits spontaneous bursting and modulates the ATP-inhibition of KATP channels.
1999,
Pubmed
Babenko,
Sulfonylurea receptors set the maximal open probability, ATP sensitivity and plasma membrane density of KATP channels.
1999,
Pubmed
Babenko,
Pharmaco-topology of sulfonylurea receptors. Separate domains of the regulatory subunits of K(ATP) channel isoforms are required for selective interaction with K(+) channel openers.
2000,
Pubmed
Baukrowitz,
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
1998,
Pubmed
,
Xenbase
Cook,
Intracellular ATP directly blocks K+ channels in pancreatic B-cells.
,
Pubmed
Drain,
KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit.
1998,
Pubmed
,
Xenbase
Drain,
Regulation of Shaker K+ channel inactivation gating by the cAMP-dependent protein kinase.
1994,
Pubmed
,
Xenbase
Fan,
Phosphoinositides decrease ATP sensitivity of the cardiac ATP-sensitive K(+) channel. A molecular probe for the mechanism of ATP-sensitive inhibition.
1999,
Pubmed
Fan,
Anionic phospholipids activate ATP-sensitive potassium channels.
1997,
Pubmed
Gillis,
Effects of sulfonamides on a metabolite-regulated ATPi-sensitive K+ channel in rat pancreatic B-cells.
1989,
Pubmed
Gordon,
A histidine residue associated with the gate of the cyclic nucleotide-activated channels in rod photoreceptors.
1995,
Pubmed
,
Xenbase
Gribble,
The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide.
1997,
Pubmed
,
Xenbase
Gribble,
MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.
1998,
Pubmed
,
Xenbase
Inagaki,
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
1995,
Pubmed
John,
The sulphonylurea receptor SUR1 regulates ATP-sensitive mouse Kir6.2 K+ channels linked to the green fluorescent protein in human embryonic kidney cells (HEK 293).
1998,
Pubmed
Jovanovic,
Acquired resistance of a mammalian cell line to hypoxia-reoxygenation through cotransfection of Kir6.2 and SUR1 clones.
1998,
Pubmed
Koshland,
Comparison of experimental binding data and theoretical models in proteins containing subunits.
1966,
Pubmed
Koster,
ATP inhibition of KATP channels: control of nucleotide sensitivity by the N-terminal domain of the Kir6.2 subunit.
1999,
Pubmed
Lorenz,
Evidence for direct physical association between a K+ channel (Kir6.2) and an ATP-binding cassette protein (SUR1) which affects cellular distribution and kinetic behavior of an ATP-sensitive K+ channel.
1998,
Pubmed
Loussouarn,
Structure and dynamics of the pore of inwardly rectifying K(ATP) channels.
2000,
Pubmed
MONOD,
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
1965,
Pubmed
McIntosh,
Mutagenesis of segment 487Phe-Ser-Arg-Asp-Arg-Lys492 of sarcoplasmic reticulum Ca2+-ATPase produces pumps defective in ATP binding.
1996,
Pubmed
Mikhailov,
Expression of functionally active ATP-sensitive K-channels in insect cells using baculovirus.
1998,
Pubmed
,
Xenbase
Nichols,
ATP dependence of KATP channel kinetics in isolated membrane patches from rat ventricle.
1991,
Pubmed
Nichols,
Adenosine diphosphate as an intracellular regulator of insulin secretion.
1996,
Pubmed
Noma,
ATP-regulated K+ channels in cardiac muscle.
,
Pubmed
Paoletti,
C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating.
1999,
Pubmed
Proks,
Involvement of the N-terminus of Kir6.2 in the inhibition of the KATP channel by ATP.
1999,
Pubmed
,
Xenbase
Qin,
Kinetics of ATP-sensitive K+ channel revealed with oil-gate concentration jump method.
1989,
Pubmed
Reidhaar-Olson,
Random mutagenesis of protein sequences using oligonucleotide cassettes.
1991,
Pubmed
Reimann,
Involvement of the n-terminus of Kir6.2 in coupling to the sulphonylurea receptor.
1999,
Pubmed
,
Xenbase
Schwanstecher,
Potassium channel openers require ATP to bind to and act through sulfonylurea receptors.
1998,
Pubmed
Shyng,
Membrane phospholipid control of nucleotide sensitivity of KATP channels.
1998,
Pubmed
Shyng,
Regulation of KATP channel activity by diazoxide and MgADP. Distinct functions of the two nucleotide binding folds of the sulfonylurea receptor.
1997,
Pubmed
Shyng,
Octameric stoichiometry of the KATP channel complex.
1997,
Pubmed
Trapp,
Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP.
1998,
Pubmed
,
Xenbase
Trube,
Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cell-attached patches.
1984,
Pubmed
Tucker,
Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2.
1999,
Pubmed
Tucker,
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
1997,
Pubmed
,
Xenbase
Tucker,
Molecular determinants of KATP channel inhibition by ATP.
1998,
Pubmed
,
Xenbase
Zagotta,
Structure and function of cyclic nucleotide-gated channels.
1996,
Pubmed
Zong,
Three amino acids in the C-linker are major determinants of gating in cyclic nucleotide-gated channels.
1998,
Pubmed
