7mit - Revision history

OCA at 13:43, 6 November 2024

2024-11-06T13:43:50Z

← Older revision		Revision as of 13:43, 6 November 2024
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	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	Vascular tone is dependent on smooth muscle ~~KATP~~ channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantu syndrome. Unique among ~~KATP~~ isoforms, they lack spontaneous activity and require Mg-nucleotides for activation. Structural mechanisms underlying these properties are unknown. Here, we determined cryogenic electron microscopy structures of vascular ~~KATP~~ channels bound to inhibitory ATP and glibenclamide, which differ informatively from similarly determined pancreatic ~~KATP~~ channel isoform (Kir6.2/SUR1). Unlike SUR1, SUR2B subunits adopt distinct rotational "propeller" and "quatrefoil" geometries surrounding their Kir6.1 core. The glutamate/aspartate-rich linker connecting the two halves of the SUR-ABC core is observed in a quatrefoil-like conformation. Molecular dynamics simulations reveal MgADP-dependent dynamic tripartite interactions between this linker, SUR2B, and Kir6.1. The structures captured implicate a progression of intermediate states between MgADP-free inactivated, and MgADP-bound activated conformations wherein the glutamate/aspartate-rich linker participates as mobile autoinhibitory domain, suggesting a conformational pathway toward ~~KATP~~ channel activation.		Vascular tone is dependent on smooth muscle K(ATP) channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantu syndrome. Unique among K(ATP) isoforms, they lack spontaneous activity and require Mg-nucleotides for activation. Structural mechanisms underlying these properties are unknown. Here, we determined cryogenic electron microscopy structures of vascular K(ATP) channels bound to inhibitory ATP and glibenclamide, which differ informatively from similarly determined pancreatic K(ATP) channel isoform (Kir6.2/SUR1). Unlike SUR1, SUR2B subunits adopt distinct rotational "propeller" and "quatrefoil" geometries surrounding their Kir6.1 core. The glutamate/aspartate-rich linker connecting the two halves of the SUR-ABC core is observed in a quatrefoil-like conformation. Molecular dynamics simulations reveal MgADP-dependent dynamic tripartite interactions between this linker, SUR2B, and Kir6.1. The structures captured implicate a progression of intermediate states between MgADP-free inactivated, and MgADP-bound activated conformations wherein the glutamate/aspartate-rich linker participates as mobile autoinhibitory domain, suggesting a conformational pathway toward K(ATP) channel activation.

	Vascular ~~KATP~~ channel structural dynamics reveal regulatory mechanism by Mg-nucleotides.,Sung MW, Yang Z, Driggers CM, Patton BL, Mostofian B, Russo JD, Zuckerman DM, Shyng SL Proc Natl Acad Sci U S A. 2021 Nov 2;118(44)~~. pii~~: ~~2109441118~~. doi:, 10.1073/pnas.2109441118. PMID:34711681<ref>PMID:34711681</ref>		Vascular K(ATP) channel structural dynamics reveal regulatory mechanism by Mg-nucleotides.,Sung MW, Yang Z, Driggers CM, Patton BL, Mostofian B, Russo JD, Zuckerman DM, Shyng SL Proc Natl Acad Sci U S A. 2021 Nov 2;118(44):e2109441118. doi: , 10.1073/pnas.2109441118. PMID:34711681<ref>PMID:34711681</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

OCA at 10:09, 16 August 2023

2023-08-16T10:09:36Z

← Older revision		Revision as of 10:09, 16 August 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7mit]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MIT FirstGlance]. <br>		<table><tr><td colspan='2'>[[7mit]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MIT FirstGlance]. <br>
	</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=GBM:5-CHLORO-N-(2-{4-[(CYCLOHEXYLCARBAMOYL)SULFAMOYL]PHENYL}ETHYL)-2-METHOXYBENZAMIDE'>GBM</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.4Å</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=GBM:5-CHLORO-N-(2-{4-[(CYCLOHEXYLCARBAMOYL)SULFAMOYL]PHENYL}ETHYL)-2-METHOXYBENZAMIDE'>GBM</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=7mit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mit OCA], [https://pdbe.org/7mit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mit RCSB], [https://www.ebi.ac.uk/pdbsum/7mit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mit ProSAT]</span></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=7mit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mit OCA], [https://pdbe.org/7mit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mit RCSB], [https://www.ebi.ac.uk/pdbsum/7mit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mit ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:22, 26 October 2022

2022-10-26T06:22:50Z

← Older revision		Revision as of 06:22, 26 October 2022
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	====		==Vascular KATP channel: Kir6.1 SUR2B propeller-like conformation 1==
	<StructureSection load='7mit' size='340' side='right'caption='[[7mit]]' scene=''>		<StructureSection load='7mit' size='340' side='right'caption='[[7mit]], [[Resolution\|resolution]] 3.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>		<table><tr><td colspan='2'>[[7mit]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MIT FirstGlance]. <br>
	</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=7mit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mit OCA], [https://pdbe.org/7mit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mit RCSB], [https://www.ebi.ac.uk/pdbsum/7mit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mit ProSAT]</span></td></tr>		</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=GBM:5-CHLORO-N-(2-{4-[(CYCLOHEXYLCARBAMOYL)SULFAMOYL]PHENYL}ETHYL)-2-METHOXYBENZAMIDE'>GBM</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=7mit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mit OCA], [https://pdbe.org/7mit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mit RCSB], [https://www.ebi.ac.uk/pdbsum/7mit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mit ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/KCNJ8_RAT KCNJ8_RAT] This potassium channel 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 external barium.<ref>PMID:7890693</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Vascular tone is dependent on smooth muscle KATP channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantu syndrome. Unique among KATP isoforms, they lack spontaneous activity and require Mg-nucleotides for activation. Structural mechanisms underlying these properties are unknown. Here, we determined cryogenic electron microscopy structures of vascular KATP channels bound to inhibitory ATP and glibenclamide, which differ informatively from similarly determined pancreatic KATP channel isoform (Kir6.2/SUR1). Unlike SUR1, SUR2B subunits adopt distinct rotational "propeller" and "quatrefoil" geometries surrounding their Kir6.1 core. The glutamate/aspartate-rich linker connecting the two halves of the SUR-ABC core is observed in a quatrefoil-like conformation. Molecular dynamics simulations reveal MgADP-dependent dynamic tripartite interactions between this linker, SUR2B, and Kir6.1. The structures captured implicate a progression of intermediate states between MgADP-free inactivated, and MgADP-bound activated conformations wherein the glutamate/aspartate-rich linker participates as mobile autoinhibitory domain, suggesting a conformational pathway toward KATP channel activation.

			Vascular KATP channel structural dynamics reveal regulatory mechanism by Mg-nucleotides.,Sung MW, Yang Z, Driggers CM, Patton BL, Mostofian B, Russo JD, Zuckerman DM, Shyng SL Proc Natl Acad Sci U S A. 2021 Nov 2;118(44). pii: 2109441118. doi:, 10.1073/pnas.2109441118. PMID:34711681<ref>PMID:34711681</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7mit" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Potassium channel 3D structures\|Potassium channel 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Z-disk~~]]		[[Category: Rattus norvegicus]]
			[[Category: Shyng SL]]
			[[Category: Sung MW]]

OCA at 11:42, 13 October 2021

2021-10-13T11:42:48Z

← Older revision		Revision as of 11:42, 13 October 2021
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7mit is ~~ON HOLD until Paper Publication~~		====
			<StructureSection load='7mit' size='340' side='right'caption='[[7mit]]' scene=''>
	~~Authors:~~		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
	~~Description~~:		</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=7mit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mit OCA], [https://pdbe.org/7mit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mit RCSB], [https://www.ebi.ac.uk/pdbsum/7mit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mit ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Z-disk]]

OCA at 07:54, 26 May 2021

2021-05-26T07:54:39Z

← Older revision		Revision as of 07:54, 26 May 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7mit is ON HOLD		The entry 7mit is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7mit" [edit=sysop:move=sysop]

2021-04-28T04:19:35Z

Protected "7mit" [edit=sysop:move=sysop]

← Older revision	Revision as of 04:19, 28 April 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7mit is ON HOLD Authors: Description: Category: Unreleased Structures

2021-04-28T04:19:34Z

New page: '''Unreleased structure''' The entry 7mit is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7mit is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]