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New page: '''Unreleased structure''' The entry 6wou is ON HOLD Authors: Description: Category: Unreleased Structures
 
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'''Unreleased structure'''


The entry 6wou is ON HOLD
==Cryo-EM structure of recombinant mouse Ryanodine Receptor type 2 mutant R176Q in complex with FKBP12.6 in nanodisc==
<StructureSection load='6wou' size='340' side='right'caption='[[6wou]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wou]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WOU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WOU 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]] 3.27&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=6wou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wou OCA], [https://pdbe.org/6wou PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wou RCSB], [https://www.ebi.ac.uk/pdbsum/6wou PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wou ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RYR2_MOUSE RYR2_MOUSE] Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.<ref>PMID:10473538</ref> <ref>PMID:9628868</ref> <ref>PMID:21098440</ref> <ref>PMID:20431056</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mutations in ryanodine receptors (RyRs), intracellular Ca(2+) channels, are associated with deadly disorders. Despite abundant functional studies, the molecular mechanism of RyR malfunction remains elusive. We studied two single-point mutations at an equivalent site in the skeletal (RyR1 R164C) and cardiac (RyR2 R176Q) isoforms using ryanodine binding, Ca(2+) imaging, and cryo-electron microscopy (cryo-EM) of the full-length protein. Loss of the positive charge had greater effect on the skeletal isoform, mediated via distortion of a salt bridge network, a molecular latch inducing rotation of a cytoplasmic domain, and partial progression to open-state traits of the large cytoplasmic assembly accompanied by alteration of the Ca(2+) binding site, which concur with the major "hyperactive" feature of the mutated channel. Our cryo-EM studies demonstrated the allosteric effect of a mutation situated ~85 A away from the pore and identified an isoform-specific structural effect.


Authors:  
Structural mechanism of two gain-of-function cardiac and skeletal RyR mutations at an equivalent site by cryo-EM.,Iyer KA, Hu Y, Nayak AR, Kurebayashi N, Murayama T, Samso M Sci Adv. 2020 Jul 29;6(31):eabb2964. doi: 10.1126/sciadv.abb2964. eCollection , 2020 Jul. PMID:32832689<ref>PMID:32832689</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6wou" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[FKBP 3D structures|FKBP 3D structures]]
*[[Ryanodine receptor 3D structures|Ryanodine receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Hu Y]]
[[Category: Iyer KA]]
[[Category: Kurebayashi N]]
[[Category: Murayama T]]
[[Category: Samso M]]
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