OCA at 03:53, 8 September 2022

2022-09-08T03:53:44Z

←Older revision		Revision as of 03:53, 8 September 2022
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-	====	+	==Rabbit RyR1 disease mutant Y523S in complex with FKBP12.6 embedded in lipidic nanodisc in the open state==
-	<StructureSection load='7t65' size='340' side='right'caption='[[7t65]]' scene=''>	+	<StructureSection load='7t65' size='340' side='right'caption='[[7t65]], [[Resolution\|resolution]] 4.05Å' 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'>[[7t65]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T65 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=7t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t65 OCA], [https://pdbe.org/7t65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t65 RCSB], [https://www.ebi.ac.uk/pdbsum/7t65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t65 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t65 OCA], [https://pdbe.org/7t65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t65 RCSB], [https://www.ebi.ac.uk/pdbsum/7t65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t65 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/RYR1_RABIT RYR1_RABIT]] Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).<ref>PMID:10388749</ref> <ref>PMID:22036948</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Ryanodine receptors (RyRs) are main regulators of intracellular Ca(2+) release and muscle contraction. The Y522S mutation of RyR1 causes central core disease, a weakening myopathy, and malignant hyperthermia, a sudden and potentially fatal response to anesthetics or heat. Y522 is in the core of the N-terminal subdomain C of RyR1 and the mechanism of how this mutation orchestrates malfunction is unpredictable for this 2-MDa ion channel, which has four identical subunits composed of 15 distinct cytoplasmic domains each. We expressed and purified the RyR1 rabbit homolog, Y523S, from HEK293 cells and reconstituted it in nanodiscs under closed and open states. The high-resolution cryogenic electron microscopic (cryo-EM) three-dimensional (3D) structures show that the phenyl ring of Tyr functions in a manner analogous to a "spacer" within an alpha-helical bundle. Mutation to the much smaller Ser alters the hydrophobic network within the bundle, triggering rearrangement of its alpha-helices with repercussions in the orientation of most cytoplasmic domains. Examining the mutation-induced readjustments exposed a series of connected alpha-helices acting as an approximately 100 A-long lever: One end protrudes toward the dihydropyridine receptor, its molecular activator (akin to an antenna), while the other end reaches the Ca(2+) activation site. The Y523S mutation elicits channel preactivation in the absence of any activator and full opening at 1.5 microM free Ca(2+), increasing by approximately 20-fold the potency of Ca(2+) to activate the channel compared with RyR1 wild type (WT). This study identified a preactivated pathological state of RyR1 and a long-range lever that may work as a molecular switch to open the channel.
		+
		+	Molecular mechanism of the severe MH/CCD mutation Y522S in skeletal ryanodine receptor (RyR1) by cryo-EM.,Iyer KA, Hu Y, Klose T, Murayama T, Samso M Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2122140119. doi:, 10.1073/pnas.2122140119. Epub 2022 Jul 22. PMID:35867837<ref>PMID:35867837</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7t65" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Oryctolagus cuniculus]]
		+	[[Category: Hu Y]]
		+	[[Category: Iyer KA]]
		+	[[Category: Murayama T]]
		+	[[Category: Samso M]]

OCA at 06:52, 20 July 2022

2022-07-20T06:52:10Z

←Older revision		Revision as of 06:52, 20 July 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7t65 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7t65' size='340' side='right'caption='[[7t65]]' 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=7t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t65 OCA], [https://pdbe.org/7t65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t65 RCSB], [https://www.ebi.ac.uk/pdbsum/7t65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t65 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 12:02, 29 December 2021

2021-12-29T12:02:40Z

←Older revision		Revision as of 12:02, 29 December 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7t65 is ON HOLD	+	The entry 7t65 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7t65" [edit=sysop:move=sysop]

2021-12-22T14:06:24Z

Protected "7t65" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:06, 22 December 2021

OCA: New page: '''Unreleased structure''' The entry 7t65 is ON HOLD Authors: Description: Category: Unreleased Structures

2021-12-22T14:06:23Z

New page: '''Unreleased structure''' The entry 7t65 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7t65 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7t65 - Revision history

OCA at 03:53, 8 September 2022

OCA at 06:52, 20 July 2022

OCA at 12:02, 29 December 2021

OCA: Protected "7t65" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7t65 is ON HOLD Authors: Description: Category: Unreleased Structures