- PDB-7ua4: Structure of PKA phosphorylated human RyR2-R2474S in the open sta... -
+
Open data
ID or keywords:
Loading...
-
Basic information
Entry
Database: PDB / ID: 7ua4
Title
Structure of PKA phosphorylated human RyR2-R2474S in the open state in the presence of Calmodulin
Components
Calmodulin-1
Peptidyl-prolyl cis-trans isomerase FKBP1B
Ryanodine receptor 2
Keywords
MEMBRANE PROTEIN / Ryanodine receptor 2 / 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 / CaM pathway / Cam-PDE 1 activation / calcium ion transport into cytosol / Sodium/Calcium exchangers / regulation of cardiac muscle contraction by calcium ion signaling / response to caffeine / cell communication by electrical coupling involved in cardiac conduction / Calmodulin induced events / response to redox state / protein maturation by protein folding / Reduction of cytosolic Ca++ levels / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / 'de novo' protein folding / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / negative regulation of heart rate / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / Activation of RAC1 downstream of NMDARs / mitochondrion-endoplasmic reticulum membrane tethering / CLEC7A (Dectin-1) induces NFAT activation / regulation of cardiac muscle cell action potential / autophagosome membrane docking / negative regulation of phosphoprotein phosphatase activity / positive regulation of heart rate / FK506 binding / positive regulation of ryanodine-sensitive calcium-release channel activity / positive regulation of axon regeneration / regulation of cell communication by electrical coupling involved in cardiac conduction / Negative regulation of NMDA receptor-mediated neuronal transmission / negative regulation of peptidyl-threonine phosphorylation / cellular response to caffeine / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / Phase 0 - rapid depolarisation / protein kinase A regulatory subunit binding / protein phosphatase activator activity / intracellularly gated calcium channel activity / RHO GTPases activate PAKs / protein kinase A catalytic subunit binding / positive regulation of the force of heart contraction / positive regulation of cyclic-nucleotide phosphodiesterase activity / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / Long-term potentiation / Uptake and function of anthrax toxins / : / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / DARPP-32 events / detection of calcium ion / smooth muscle contraction / smooth endoplasmic reticulum / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / response to vitamin E / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction / calcium channel inhibitor activity / cellular response to interferon-beta / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / protein peptidyl-prolyl isomerization / eNOS activation / Activation of AMPK downstream of NMDARs / 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 Similarity search - Function
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
R01HL145473
United States
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.
pH: 7.4 Details: Xanthine was made fresh to avoid aggregation. Xanthine stock solution was 10 mM in NaOH 0.5 N.
Buffer component
ID
Conc.
Name
Formula
Buffer-ID
1
230mM
sodiumchloride
NaClSodium chloride
1
2
10mM
HEPES
HEPES
1
3
0.4 %
CHAPS
CHAPS
1
4
1mM
EGTA
EGTA
1
5
0.5mM
TCEP
TCEP
1
6
0.001 %
DOPC
DOPC
1
7
10mM
ATPAdenosine triphosphate
ATPAdenosine triphosphate
1
8
0.2mM
cAMP
cAMP
1
9
0.65mM
Calcium
Ca(II)
1
10
0.5mM
Xanthine
Xanthine
1
Specimen
Conc.: 2.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: 40 uM of Calmodulin was added to the final sample.
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator
Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.
Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi