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.
Remodelling of the SUR-Kir6.2 interface of the KATP channel upon ATP binding revealed by the conformational blocker rhodamine 123.
Hosy E
,
Dérand R
,
Revilloud J
,
Vivaudou M
.
???displayArticle.abstract???
ATP-sensitive K+ channels (K(ATP) channels) are metabolic sensors formed by association of a K+ channel, Kir6, and an ATP-binding cassette (ABC) protein, SUR, which allosterically regulates channel gating in response to nucleotides and pharmaceutical openers and blockers. How nucleotide binding to SUR translates into modulation of Kir6 gating remains largely unknown. To address this issue, we have used a novel conformational KATP channel inhibitor, rhodamine 123 (Rho123) which targets the Kir6 subunit in a SUR-dependent manner. Rho123 blocked SUR-less Kir6.2 channels with an affinity of approximately 1 microM, regardless of the presence of nucleotides, but it had no effect on channels formed by the association of Kir6.2 and the N-terminal transmembrane domain TMD0 of SUR. Rho123 blocked SUR + Kir6.2 channels with the same affinity as Kir6.2 but this effect was antagonized by ATP. Protection from Rho123 block by ATP was due to direct binding of ATP to SUR and did not entail hydrolysis because it was not mimicked by AMP, did not require Mg2+ and was reduced by mutations in the nucleotide-binding domains of SUR. These results suggest that Rho123 binds at the TMD0-Kir6.2 interface and that binding of ATP to SUR triggers a change in the structure of the contact zone between Kir6.2 and domain TMD0 of SUR that causes masking of the Rho123 site on Kir6.2.
Babenko,
Sur domains that associate with and gate KATP pores define a novel gatekeeper.
2003, Pubmed
Babenko,
Sur domains that associate with and gate KATP pores define a novel gatekeeper.
2003,
Pubmed
Bakos,
Functional multidrug resistance protein (MRP1) lacking the N-terminal transmembrane domain.
1998,
Pubmed
Baukrowitz,
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
1998,
Pubmed
,
Xenbase
Booth,
Analysis of the properties of the N-terminal nucleotide-binding domain of human P-glycoprotein.
2000,
Pubmed
Bouabe,
The distinct nucleotide binding states of the transporter associated with antigen processing (TAP) are regulated by the nonhomologous C-terminal tails of TAP1 and TAP2.
2003,
Pubmed
Bryan,
Toward linking structure with function in ATP-sensitive K+ channels.
2004,
Pubmed
Chan,
N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits.
2003,
Pubmed
,
Xenbase
Chen,
A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle.
2003,
Pubmed
Daoud,
Rhodamine 123 binds to multiple sites in the multidrug resistance protein (MRP1).
2000,
Pubmed
Fan,
Anionic phospholipids activate ATP-sensitive potassium channels.
1997,
Pubmed
Fang,
The N-terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of sulphonylurea receptor define the unique intrinsic gating of KATP channels.
2006,
Pubmed
,
Xenbase
Furukawa,
Mechanism for reactivation of the ATP-sensitive K+ channel by MgATP complexes in guinea-pig ventricular myocytes.
1994,
Pubmed
Gribble,
MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.
1998,
Pubmed
,
Xenbase
Hopfner,
Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily.
2000,
Pubmed
Hou,
Allosteric interactions between the two non-equivalent nucleotide binding domains of multidrug resistance protein MRP1.
2000,
Pubmed
Hrycyna,
Both ATP sites of human P-glycoprotein are essential but not symmetric.
1999,
Pubmed
Johnson,
Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy.
1981,
Pubmed
Kern,
Expression and characterization of the N- and C-terminal ATP-binding domains of MRP1.
2000,
Pubmed
Lerner-Marmarosh,
Large scale purification of detergent-soluble P-glycoprotein from Pichia pastoris cells and characterization of nucleotide binding properties of wild-type, Walker A, and Walker B mutant proteins.
1999,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Loetchutinat,
New insights into the P-glycoprotein-mediated effluxes of rhodamines.
2003,
Pubmed
Matsuo,
Different binding properties and affinities for ATP and ADP among sulfonylurea receptor subtypes, SUR1, SUR2A, and SUR2B.
2000,
Pubmed
Matsuo,
KATP channel interaction with adenine nucleotides.
2005,
Pubmed
Mikhailov,
3-D structural and functional characterization of the purified KATP channel complex Kir6.2-SUR1.
2005,
Pubmed
Modica-Napolitano,
Basis for the selective cytotoxicity of rhodamine 123.
1987,
Pubmed
Moreau,
The molecular basis of the specificity of action of K(ATP) channel openers.
2000,
Pubmed
Moreau,
The size of a single residue of the sulfonylurea receptor dictates the effectiveness of K ATP channel openers.
2005,
Pubmed
Moreau,
SUR, ABC proteins targeted by KATP channel openers.
2005,
Pubmed
Nichols,
Adenosine diphosphate as an intracellular regulator of insulin secretion.
1996,
Pubmed
Nichols,
KATP channels as molecular sensors of cellular metabolism.
2006,
Pubmed
Ribalet,
Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.
2003,
Pubmed
Seino,
Physiological and pathophysiological roles of ATP-sensitive K+ channels.
2003,
Pubmed
Shyng,
Membrane phospholipid control of nucleotide sensitivity of KATP channels.
1998,
Pubmed
Smith,
ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer.
2002,
Pubmed
Tarasov,
Metabolic regulation of the pancreatic beta-cell ATP-sensitive K+ channel: a pas de deux.
2004,
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
Ueda,
MgADP antagonism to Mg2+-independent ATP binding of the sulfonylurea receptor SUR1.
1997,
Pubmed
Urbatsch,
Mutations in either nucleotide-binding site of P-glycoprotein (Mdr3) prevent vanadate trapping of nucleotide at both sites.
1998,
Pubmed
Vivaudou,
Modification by protons of frog skeletal muscle KATP channels: effects on ion conduction and nucleotide inhibition.
1995,
Pubmed
Walker,
Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.
1982,
Pubmed
Weber,
Mg2+ coordination in catalytic sites of F1-ATPase.
1998,
Pubmed
Wolters,
Selective and ATP-dependent translocation of peptides by the homodimeric ATP binding cassette transporter TAP-like (ABCB9).
2005,
Pubmed
Yamada,
Mutation in nucleotide-binding domains of sulfonylurea receptor 2 evokes Na-ATP-dependent activation of ATP-sensitive K+ channels: implication for dimerization of nucleotide-binding domains to induce channel opening.
2004,
Pubmed
Yamada,
A functional role of the C-terminal 42 amino acids of SUR2A and SUR2B in the physiology and pharmacology of cardiovascular ATP-sensitive K(+) channels.
2005,
Pubmed
Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase
Zingman,
Signaling in channel/enzyme multimers: ATPase transitions in SUR module gate ATP-sensitive K+ conductance.
2001,
Pubmed