+Open data
-Basic information
Entry | Database: PDB / ID: 7ua9 | ||||||
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Title | Structure of dephosphorylated human RyR2 in the open state | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / calcium channel | ||||||
Function / homology | Function and homology information junctional sarcoplasmic reticulum membrane / suramin binding / establishment of protein localization to endoplasmic reticulum / type B pancreatic cell apoptotic process / Purkinje myocyte to ventricular cardiac muscle cell signaling / regulation of SA node cell action potential / regulation of atrial cardiac muscle cell action potential / left ventricular cardiac muscle tissue morphogenesis / regulation of AV node cell action potential / positive regulation of ATPase-coupled calcium transmembrane transporter activity ...junctional sarcoplasmic reticulum membrane / suramin binding / establishment of protein localization to endoplasmic reticulum / type B pancreatic cell apoptotic process / Purkinje myocyte to ventricular cardiac muscle cell signaling / regulation of SA node cell action potential / regulation of atrial cardiac muscle cell action potential / left ventricular cardiac muscle tissue morphogenesis / regulation of AV node cell action potential / positive regulation of ATPase-coupled calcium transmembrane transporter activity / calcium-induced calcium release activity / sarcoplasmic reticulum calcium ion transport / ventricular cardiac muscle cell action potential / regulation of ventricular cardiac muscle cell action potential / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / embryonic heart tube morphogenesis / cardiac muscle hypertrophy / negative regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of release of sequestered calcium ion into cytosol / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / response to muscle activity / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / calcium ion transport into cytosol / regulation of cardiac muscle contraction by calcium ion signaling / response to caffeine / cell communication by electrical coupling involved in cardiac conduction / response to redox state / protein maturation by protein folding / 'de novo' protein folding / negative regulation of heart rate / negative regulation of phosphoprotein phosphatase activity / positive regulation of heart rate / FK506 binding / positive regulation of axon regeneration / cellular response to caffeine / protein kinase A regulatory subunit binding / intracellularly gated calcium channel activity / protein kinase A catalytic subunit binding / positive regulation of the force of heart contraction / : / detection of calcium ion / smooth muscle contraction / smooth endoplasmic reticulum / negative regulation of ryanodine-sensitive calcium-release channel activity / response to vitamin E / regulation of cardiac muscle contraction / calcium channel inhibitor activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / protein peptidyl-prolyl isomerization / T cell proliferation / striated muscle contraction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / release of sequestered calcium ion into cytosol / cardiac muscle contraction / Ion homeostasis / regulation of ryanodine-sensitive calcium-release channel activity / sarcoplasmic reticulum membrane / cellular response to epinephrine stimulus / calcium channel complex / regulation of cytosolic calcium ion concentration / response to muscle stretch / regulation of heart rate / sarcoplasmic reticulum / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / establishment of localization in cell / calcium-mediated signaling / calcium channel activity / response to hydrogen peroxide / Stimuli-sensing channels / sarcolemma / Z disc / intracellular calcium ion homeostasis / calcium ion transport / : / positive regulation of cytosolic calcium ion concentration / protein refolding / transmembrane transporter binding / calmodulin binding / response to hypoxia / signaling receptor binding / calcium ion binding / enzyme binding / protein-containing complex / membrane / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.59 Å | ||||||
Authors | Miotto, M.C. / Marks, A.R. | ||||||
Funding support | United States, 1items
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Citation | Journal: Sci Adv / Year: 2022 Title: Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment. Authors: Marco C Miotto / Gunnar Weninger / Haikel Dridi / Qi Yuan / Yang Liu / Anetta Wronska / Zephan Melville / Leah Sittenfeld / Steven Reiken / Andrew R Marks / Abstract: 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 ...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 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 Å, and reaching local resolutions of 2.25 Å, 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 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ua9.cif.gz | 3 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7ua9.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7ua9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ua/7ua9 ftp://data.pdbj.org/pub/pdb/validation_reports/ua/7ua9 | HTTPS FTP |
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-Related structure data
Related structure data | 26416MC 7u9qC 7u9rC 7u9tC 7u9xC 7u9zC 7ua1C 7ua3C 7ua4C 7ua5C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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