6j6l
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
==Crystal structure of mouse Ryanodine Receptor 2 SPRY1 Domain (650-844) disease mutant I784F== | ==Crystal structure of mouse Ryanodine Receptor 2 SPRY1 Domain (650-844) disease mutant I784F== | ||
| - | <StructureSection load='6j6l' size='340' side='right'caption='[[6j6l]]' scene=''> | + | <StructureSection load='6j6l' size='340' side='right'caption='[[6j6l]], [[Resolution|resolution]] 1.45Å' 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=6J6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6J6L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6j6l]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6J6L 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=6j6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j6l OCA], [https://pdbe.org/6j6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6j6l RCSB], [https://www.ebi.ac.uk/pdbsum/6j6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6j6l ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.452Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</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=6j6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j6l OCA], [https://pdbe.org/6j6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6j6l RCSB], [https://www.ebi.ac.uk/pdbsum/6j6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6j6l ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | Idiopathic ventricular fibrillation (IVF) causes sudden death in young adult patients without structural or ischemic heart disease. Most IVF cases are sporadic and some patients present with short-coupled torsade de pointes, the genetics of which are poorly understood. A man who had a first syncope at the age of 35 presented with frequent short-coupled premature ventricular beats with bursts of polymorphic ventricular tachycardia and then died suddenly. By exome sequencing, we identified three rare variants: p.I784F in the SPRY1 of the ryanodine receptor 2 (RyR2), p.A96S in connexin 40 (Cx40), reported to affect electrical coupling and cardiac conduction, and a nonsense p.R244X in the cardiac-specific troponin I-interacting kinase (TNNI3K). We assessed intracellular Ca(2+) handling in WT and mutant human RYR2 transfected HEK293 cells by fluorescent microscopy and an enhanced store overload-induced Ca(2+) release in response to cytosolic Ca(2+) was observed in RyR2-I784F cells. In addition, crystal structures and thermal melting temperatures revealed a conformational change in the I784F-SPRY1 domain compared to the WT-domain. The novel RyR2-I784F variant in SPRY1 domain causes a leaky channel under non-stress conditions. The presence of several variants affecting Ca(2+) handling and cardiac conduction suggests a possible oligogenic origin for the ectopies originating from Purkinje fibres. | ||
| + | |||
| + | A SPRY1 domain cardiac ryanodine receptor variant associated with short-coupled torsade de pointes.,Touat-Hamici Z, Blancard M, Ma R, Lin L, Iddir Y, Denjoy I, Leenhardt A, Yuchi Z, Guicheney P Sci Rep. 2021 Mar 4;11(1):5243. doi: 10.1038/s41598-021-84373-9. PMID:33664309<ref>PMID:33664309</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6j6l" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Ryanodine receptor 3D structures|Ryanodine receptor 3D structures]] | *[[Ryanodine receptor 3D structures|Ryanodine receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
[[Category: Lin L]] | [[Category: Lin L]] | ||
[[Category: Ma R]] | [[Category: Ma R]] | ||
[[Category: Yuchi Z]] | [[Category: Yuchi Z]] | ||
Current revision
Crystal structure of mouse Ryanodine Receptor 2 SPRY1 Domain (650-844) disease mutant I784F
| |||||||||||
Categories: Large Structures | Mus musculus | Lin L | Ma R | Yuchi Z
