+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26205 | |||||||||||||||||||||
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Title | A drug and ATP binding site in type 1 ryanodine receptor | |||||||||||||||||||||
Map data | Composite map | |||||||||||||||||||||
Sample |
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Function / homology | Function and homology information cytoplasmic side of membrane / ATP-gated ion channel activity / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / ossification involved in bone maturation ...cytoplasmic side of membrane / ATP-gated ion channel activity / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / ossification involved in bone maturation / Calmodulin induced events / Reduction of cytosolic Ca++ levels / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / 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 / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / 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 / Activation of RAC1 downstream of NMDARs / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Negative regulation of NMDA receptor-mediated neuronal transmission / cellular response to caffeine / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / outflow tract morphogenesis / Phase 0 - rapid depolarisation / intracellularly gated calcium channel activity / protein phosphatase activator 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 / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / catalytic complex / DARPP-32 events / detection of calcium ion / 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 / 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 / eNOS activation / skeletal muscle fiber development / striated muscle contraction / Activation of AMPK downstream of NMDARs / 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 / positive regulation of protein dephosphorylation / Ion homeostasis / regulation of calcium-mediated signaling / regulation of ryanodine-sensitive calcium-release channel activity / titin binding / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / sperm midpiece / sarcoplasmic reticulum membrane / calcium channel complex / cellular response to calcium ion / substantia nigra development / adenylate cyclase activator activity / Ras activation upon Ca2+ influx through NMDA receptor / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / VEGFR2 mediated vascular permeability / regulation of cytokinesis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / positive regulation of peptidyl-threonine phosphorylation / VEGFR2 mediated cell proliferation / peptidylprolyl isomerase / sarcoplasmic reticulum / peptidyl-prolyl cis-trans isomerase activity / muscle contraction / Translocation of SLC2A4 (GLUT4) to the plasma membrane / calcium ion transmembrane transport / positive regulation of receptor signaling pathway via JAK-STAT Similarity search - Function | |||||||||||||||||||||
Biological species | Oryctolagus cuniculus (rabbit) / Homo sapiens (human) / rabbit (rabbit) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.45 Å | |||||||||||||||||||||
Authors | Melville Z / Dridi H / Yuan Q / Reiken S / Anetta W / Liu Y / Clarke OB / Marks AR | |||||||||||||||||||||
Funding support | United States, 6 items
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Citation | Journal: Structure / Year: 2022 Title: A drug and ATP binding site in type 1 ryanodine receptor. Authors: Zephan Melville / Haikel Dridi / Qi Yuan / Steven Reiken / Anetta Wronska / Yang Liu / Oliver B Clarke / Andrew R Marks / Abstract: The ryanodine receptor (RyR)/calcium release channel on the sarcoplasmic reticulum (SR) is required for excitation-contraction coupling in skeletal and cardiac muscle. Inherited mutations and stress- ...The ryanodine receptor (RyR)/calcium release channel on the sarcoplasmic reticulum (SR) is required for excitation-contraction coupling in skeletal and cardiac muscle. Inherited mutations and stress-induced post-translational modifications result in an SR Ca leak that causes skeletal myopathies, heart failure, and exercise-induced sudden death. A class of therapeutics known as Rycals prevent the RyR-mediated leak, are effective in preventing disease progression and restoring function in animal models, and are in clinical trials for patients with muscle and heart disorders. Using cryogenic-electron microscopy, we present a model of RyR1 with a 2.45-Å resolution before local refinement, revealing a binding site in the RY1&2 domain (3.10 Å local resolution), where the Rycal ARM210 binds cooperatively with ATP and stabilizes the closed state of RyR1. | |||||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26205.map.gz | 379.9 MB | EMDB map data format | |
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Header (meta data) | emd-26205-v30.xml emd-26205.xml | 32 KB 32 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26205_fsc.xml emd_26205_fsc_2.xml | 19.1 KB 19 KB | Display Display | FSC data file |
Images | emd_26205.png | 81.3 KB | ||
Masks | emd_26205_msk_1.map emd_26205_msk_2.map emd_26205_msk_3.map | 512 MB 512 MB 512 MB | Mask map | |
Others | emd_26205_additional_1.map.gz emd_26205_half_map_1.map.gz emd_26205_half_map_2.map.gz | 256.4 MB 391.7 MB 391.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26205 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26205 | HTTPS FTP |
-Validation report
Summary document | emd_26205_validation.pdf.gz | 936.5 KB | Display | EMDB validaton report |
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Full document | emd_26205_full_validation.pdf.gz | 936.1 KB | Display | |
Data in XML | emd_26205_validation.xml.gz | 26 KB | Display | |
Data in CIF | emd_26205_validation.cif.gz | 34.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26205 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26205 | HTTPS FTP |
-Related structure data
Related structure data | 7tzcMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
EM raw data | EMPIAR-10997 (Title: A drug and ATP binding site in type 1 ryanodine receptor Data size: 1.5 TB Data #1: Type-1 ryanodine receptor [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26205.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Composite map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.833 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_26205_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Mask #2
File | emd_26205_msk_2.map | ||||||||||||
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Density Histograms |
-Mask #3
File | emd_26205_msk_3.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Initial refinement map
File | emd_26205_additional_1.map | ||||||||||||
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Annotation | Initial refinement map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_26205_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_26205_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Ryanodine receptor 1 complex with calmodulin and calstabin-1
+Supramolecule #1: Ryanodine receptor 1 complex with calmodulin and calstabin-1
+Macromolecule #1: Calmodulin-1
+Macromolecule #2: Peptidyl-prolyl cis-trans isomerase FKBP1A
+Macromolecule #3: Ryanodine receptor 1
+Macromolecule #4: CALCIUM ION
+Macromolecule #5: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #6: ZINC ION
+Macromolecule #7: CAFFEINE
+Macromolecule #8: 4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)methyl]benz...
+Macromolecule #9: (2S)-3-(octadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 8.4 mg/mL | |||||||||||||||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R0.6/1 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Support film - Film thickness: 50.0 nm | |||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 6862 / Average exposure time: 2.5 sec. / Average electron dose: 57.65 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |