7u9r: Difference between revisions
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==== | ==Structure of PKA phosphorylated human RyR2 in the open state== | ||
<StructureSection load='7u9r' size='340' side='right'caption='[[7u9r]]' scene=''> | <StructureSection load='7u9r' size='340' side='right'caption='[[7u9r]], [[Resolution|resolution]] 3.69Å' 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'>[[7u9r]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U9R 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=7u9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u9r OCA], [https://pdbe.org/7u9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u9r RCSB], [https://www.ebi.ac.uk/pdbsum/7u9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u9r 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=XAN:XANTHINE'>XAN</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=7u9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u9r OCA], [https://pdbe.org/7u9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u9r RCSB], [https://www.ebi.ac.uk/pdbsum/7u9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u9r ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/FKB1B_HUMAN FKB1B_HUMAN]] Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ryanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT results from stress-induced sarcoplasmic reticular Ca(2+) leak via the mutant RyR2 channels during diastole. We present atomic models of human wild-type (WT) RyR2 and the CPVT mutant RyR2-R2474S determined by cryo-electron microscopy with overall resolutions in the range of 2.6 to 3.6 A, and reaching local resolutions of 2.25 A, unprecedented for RyR2 channels. Under nonactivating conditions, the RyR2-R2474S channel is in a "primed" state between the closed and open states of WT RyR2, rendering it more sensitive to activation that results in stress-induced Ca(2+) leak. The Rycal drug ARM210 binds to RyR2-R2474S, reverting the primed state toward the closed state. Together, these studies provide a mechanism for CPVT and for the therapeutic actions of ARM210. | |||
Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.,Miotto MC, Weninger G, Dridi H, Yuan Q, Liu Y, Wronska A, Melville Z, Sittenfeld L, Reiken S, Marks AR Sci Adv. 2022 Jul 22;8(29):eabo1272. doi: 10.1126/sciadv.abo1272. Epub 2022 Jul, 20. PMID:35857850<ref>PMID:35857850</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7u9r" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Marks AR]] | ||
[[Category: Miotto MC]] | |||
Latest revision as of 06:19, 8 September 2022
Structure of PKA phosphorylated human RyR2 in the open stateStructure of PKA phosphorylated human RyR2 in the open state
Structural highlights
Function[FKB1B_HUMAN] Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Publication Abstract from PubMedRyanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT results from stress-induced sarcoplasmic reticular Ca(2+) leak via the mutant RyR2 channels during diastole. We present atomic models of human wild-type (WT) RyR2 and the CPVT mutant RyR2-R2474S determined by cryo-electron microscopy with overall resolutions in the range of 2.6 to 3.6 A, and reaching local resolutions of 2.25 A, unprecedented for RyR2 channels. Under nonactivating conditions, the RyR2-R2474S channel is in a "primed" state between the closed and open states of WT RyR2, rendering it more sensitive to activation that results in stress-induced Ca(2+) leak. The Rycal drug ARM210 binds to RyR2-R2474S, reverting the primed state toward the closed state. Together, these studies provide a mechanism for CPVT and for the therapeutic actions of ARM210. Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.,Miotto MC, Weninger G, Dridi H, Yuan Q, Liu Y, Wronska A, Melville Z, Sittenfeld L, Reiken S, Marks AR Sci Adv. 2022 Jul 22;8(29):eabo1272. doi: 10.1126/sciadv.abo1272. Epub 2022 Jul, 20. PMID:35857850[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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