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Yorodumi- EMDB-27736: RyR1 in presence of IpCa-T26E phosphomimetic and activating ligands -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27736 | |||||||||
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Title | RyR1 in presence of IpCa-T26E phosphomimetic and activating ligands | |||||||||
Map data | RyR1 in presence of IpCa-T26E phosphomimetic and activating ligands | |||||||||
Sample |
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Keywords | Ryanodine receptor / Ion channel / Snake toxin / Calcin / Complex / Membrane protein | |||||||||
Function / homology | Function and homology information ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / ryanodine receptor complex / 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 ...ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / ryanodine receptor complex / 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 / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / ossification involved in bone maturation / 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 / skin development / CaMK IV-mediated phosphorylation of CREB / positive regulation of cyclic-nucleotide phosphodiesterase activity / Glycogen breakdown (glycogenolysis) / negative regulation of heart rate / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / negative regulation of phosphoprotein phosphatase activity / Activation of RAC1 downstream of NMDARs / FK506 binding / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / positive regulation of axon regeneration / 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 / outflow tract morphogenesis / Phase 0 - rapid depolarisation / protein phosphatase activator activity / intracellularly gated calcium channel activity / RHO GTPases activate PAKs / organelle membrane / 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 / regulation of cardiac muscle contraction / toxic substance binding / smooth endoplasmic reticulum / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / voltage-gated calcium channel activity / response to vitamin E / calcium channel inhibitor activity / RHO GTPases activate IQGAPs / 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 / skeletal muscle fiber development / T cell proliferation / Activation of AMPK downstream of NMDARs / striated muscle contraction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / release of sequestered calcium ion into cytosol / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / regulation of calcium-mediated signaling / positive regulation of protein dephosphorylation / Ion homeostasis / titin binding / regulation of ryanodine-sensitive calcium-release channel activity / voltage-gated potassium channel complex / positive regulation of protein autophosphorylation / sperm midpiece / sarcoplasmic reticulum membrane / calcium channel complex / regulation of cytosolic calcium ion concentration / substantia nigra development / cellular response to calcium ion Similarity search - Function | |||||||||
Biological species | Oryctolagus cuniculus (rabbit) / Homo sapiens (human) / rabbit (rabbit) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.84 Å | |||||||||
Authors | Haji-Ghassemi O / Van Petegm F | |||||||||
Funding support | Canada, 2 items
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Citation | Journal: Sci Adv / Year: 2023 Title: Cryo-EM analysis of scorpion toxin binding to Ryanodine Receptors reveals subconductance that is abolished by PKA phosphorylation. Authors: Omid Haji-Ghassemi / Yu Seby Chen / Kellie Woll / Georgina B Gurrola / Carmen R Valdivia / Wenxuan Cai / Songhua Li / Hector H Valdivia / Filip Van Petegem / Abstract: Calcins are peptides from scorpion venom with the unique ability to cross cell membranes, gaining access to intracellular targets. Ryanodine Receptors (RyR) are intracellular ion channels that ...Calcins are peptides from scorpion venom with the unique ability to cross cell membranes, gaining access to intracellular targets. Ryanodine Receptors (RyR) are intracellular ion channels that control release of Ca from the endoplasmic and sarcoplasmic reticulum. Calcins target RyRs and induce long-lived subconductance states, whereby single-channel currents are decreased. We used cryo-electron microscopy to reveal the binding and structural effects of imperacalcin, showing that it opens the channel pore and causes large asymmetry throughout the cytosolic assembly of the tetrameric RyR. This also creates multiple extended ion conduction pathways beyond the transmembrane region, resulting in subconductance. Phosphorylation of imperacalcin by protein kinase A prevents its binding to RyR through direct steric hindrance, showing how posttranslational modifications made by the host organism can determine the fate of a natural toxin. The structure provides a direct template for developing calcin analogs that result in full channel block, with potential to treat RyR-related disorders. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27736.map.gz | 481.1 MB | EMDB map data format | |
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Header (meta data) | emd-27736-v30.xml emd-27736.xml | 26.4 KB 26.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27736_fsc.xml | 19.3 KB | Display | FSC data file |
Images | emd_27736.png | 85.2 KB | ||
Others | emd_27736_half_map_1.map.gz emd_27736_half_map_2.map.gz | 474.8 MB 474.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27736 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27736 | HTTPS FTP |
-Validation report
Summary document | emd_27736_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_27736_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_27736_validation.xml.gz | 26.5 KB | Display | |
Data in CIF | emd_27736_validation.cif.gz | 34.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27736 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27736 | HTTPS FTP |
-Related structure data
Related structure data | 8dveMC 8drpC 8dtbC 8dujC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_27736.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | RyR1 in presence of IpCa-T26E phosphomimetic and activating ligands | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.94 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: RyR1 in presence of IpCa-T26E phosphomimetic and activating ligands
File | emd_27736_half_map_1.map | ||||||||||||
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Annotation | RyR1 in presence of IpCa-T26E phosphomimetic and activating ligands | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: RyR1 in presence of IpCa-T26E phosphomimetic and activating ligands
File | emd_27736_half_map_2.map | ||||||||||||
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Annotation | RyR1 in presence of IpCa-T26E phosphomimetic and activating ligands | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : RyR1 complex with activating ligands in open state
+Supramolecule #1: RyR1 complex with activating ligands in open state
+Supramolecule #2: Ryanodine receptor 1
+Supramolecule #3: Peptidyl-prolyl cis-trans isomerase FKBP1B, Calmodulin-1
+Macromolecule #1: Ryanodine receptor 1
+Macromolecule #2: Peptidyl-prolyl cis-trans isomerase FKBP1B
+Macromolecule #3: Calmodulin-1
+Macromolecule #4: CAFFEINE
+Macromolecule #5: CALCIUM ION
+Macromolecule #6: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #7: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 10 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: Quantifoil R2/2 / Mesh: 300 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: TFS Selectris |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model | Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Refinement | Space: REAL / Protocol: RIGID BODY FIT / Target criteria: Correlation coefficient |
Output model | PDB-8dve: |