7u2x: Difference between revisions
New page: '''Unreleased structure''' The entry 7u2x is ON HOLD Authors: Shyng, S.L., Sung, M.W., Driggers, C.M. Description: Cryo-EM structure of the pancreatic ATP-sensitive potassium channel i... |
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The | ==Cryo-EM structure of the pancreatic ATP-sensitive potassium channel in the presence of carbamazepine and ATP with Kir6.2-CTD in the down conformation== | ||
<StructureSection load='7u2x' size='340' side='right'caption='[[7u2x]], [[Resolution|resolution]] 4.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7u2x]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetus_cricetus Cricetus cricetus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U2X FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P5S:O-[(R)-{[(2R)-2,3-BIS(OCTADECANOYLOXY)PROPYL]OXY}(HYDROXY)PHOSPHORYL]-L-SERINE'>P5S</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7u2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u2x OCA], [https://pdbe.org/7u2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u2x RCSB], [https://www.ebi.ac.uk/pdbsum/7u2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u2x ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KCJ11_RAT KCJ11_RAT] This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium. Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Regulation of pancreatic K(ATP) channels involves orchestrated interactions of their subunits, Kir6.2 and SUR1, and ligands. Previously we reported K(ATP) channel cryo-EM structures in the presence and absence of pharmacological inhibitors and ATP, focusing on the mechanisms by which inhibitors act as pharmacological chaperones of K(ATP) channels (Martin et al., 2019). Here we analyzed the same cryo-EM datasets with a focus on channel conformational dynamics to elucidate structural correlates pertinent to ligand interactions and channel gating. We found pharmacological inhibitors and ATP enrich a channel conformation in which the Kir6.2 cytoplasmic domain is closely associated with the transmembrane domain, while depleting one where the Kir6.2 cytoplasmic domain is extended away into the cytoplasm. This conformational change remodels a network of intra- and inter-subunit interactions as well as the ATP and PIP(2) binding pockets. The structures resolved key contacts between the distal N-terminus of Kir6.2 and SUR1's ABC module involving residues implicated in channel function and showed a SUR1 residue, K134, participates in PIP(2) binding. Molecular dynamics simulations revealed two Kir6.2 residues, K39 and R54, that mediate both ATP and PIP(2) binding, suggesting a mechanism for competitive gating by ATP and PIP(2). | |||
Ligand-mediated Structural Dynamics of a Mammalian Pancreatic K(ATP) Channel.,Sung MW, Driggers CM, Mostofian B, Russo JD, Patton BL, Zuckerman DM, Shyng SL J Mol Biol. 2022 Oct 15;434(19):167789. doi: 10.1016/j.jmb.2022.167789. Epub 2022 , Aug 11. PMID:35964676<ref>PMID:35964676</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Driggers | <div class="pdbe-citations 7u2x" style="background-color:#fffaf0;"></div> | ||
[[Category: Shyng | |||
[[Category: Sung | ==See Also== | ||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cricetus cricetus]] | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Driggers CM]] | |||
[[Category: Shyng SL]] | |||
[[Category: Sung MW]] | |||
Latest revision as of 17:06, 6 November 2024
Cryo-EM structure of the pancreatic ATP-sensitive potassium channel in the presence of carbamazepine and ATP with Kir6.2-CTD in the down conformationCryo-EM structure of the pancreatic ATP-sensitive potassium channel in the presence of carbamazepine and ATP with Kir6.2-CTD in the down conformation
Structural highlights
FunctionKCJ11_RAT This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium. Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (By similarity). Publication Abstract from PubMedRegulation of pancreatic K(ATP) channels involves orchestrated interactions of their subunits, Kir6.2 and SUR1, and ligands. Previously we reported K(ATP) channel cryo-EM structures in the presence and absence of pharmacological inhibitors and ATP, focusing on the mechanisms by which inhibitors act as pharmacological chaperones of K(ATP) channels (Martin et al., 2019). Here we analyzed the same cryo-EM datasets with a focus on channel conformational dynamics to elucidate structural correlates pertinent to ligand interactions and channel gating. We found pharmacological inhibitors and ATP enrich a channel conformation in which the Kir6.2 cytoplasmic domain is closely associated with the transmembrane domain, while depleting one where the Kir6.2 cytoplasmic domain is extended away into the cytoplasm. This conformational change remodels a network of intra- and inter-subunit interactions as well as the ATP and PIP(2) binding pockets. The structures resolved key contacts between the distal N-terminus of Kir6.2 and SUR1's ABC module involving residues implicated in channel function and showed a SUR1 residue, K134, participates in PIP(2) binding. Molecular dynamics simulations revealed two Kir6.2 residues, K39 and R54, that mediate both ATP and PIP(2) binding, suggesting a mechanism for competitive gating by ATP and PIP(2). Ligand-mediated Structural Dynamics of a Mammalian Pancreatic K(ATP) Channel.,Sung MW, Driggers CM, Mostofian B, Russo JD, Patton BL, Zuckerman DM, Shyng SL J Mol Biol. 2022 Oct 15;434(19):167789. doi: 10.1016/j.jmb.2022.167789. Epub 2022 , Aug 11. PMID:35964676[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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