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Yorodumi- EMDB-33936: Structure of recombinant RyR2 (EGTA dataset, class 1, closed state) -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33936 | |||||||||||||||||||||
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Title | Structure of recombinant RyR2 (EGTA dataset, class 1, closed state) | |||||||||||||||||||||
Map data | Structure of recombinant RyR2 (EGTA dataset, class 1, closed state) | |||||||||||||||||||||
Sample |
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Function / homology | Function and homology information manganese ion transmembrane transport / 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 / organic cyclic compound binding / regulation of AV node cell action potential ...manganese ion transmembrane transport / 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 / organic cyclic compound binding / regulation of AV node cell action potential / calcium-induced calcium release activity / sarcoplasmic reticulum calcium ion transport / Stimuli-sensing channels / Ion homeostasis / ventricular cardiac muscle cell action potential / regulation of ventricular cardiac muscle cell action potential / positive regulation of sequestering of calcium ion / regulation of cardiac muscle contraction by calcium ion signaling / cyclic nucleotide binding / embryonic heart tube morphogenesis / negative regulation of insulin secretion involved in cellular response to glucose stimulus / cardiac muscle hypertrophy / 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 / response to muscle activity / calcium ion transport into cytosol / calcium ion transmembrane import into cytosol / A band / 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 / FK506 binding / positive regulation of heart rate / negative regulation of cytosolic calcium ion concentration / positive regulation of axon regeneration / cellular response to caffeine / protein kinase A regulatory subunit binding / intracellularly gated calcium channel activity / smooth endoplasmic reticulum / protein kinase A catalytic subunit binding / positive regulation of the force of heart contraction / response to magnesium ion / : / detection of calcium ion / smooth muscle contraction / striated muscle contraction / 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 / 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 / calcium channel complex / cellular response to epinephrine stimulus / regulation of cytosolic calcium ion concentration / response to muscle stretch / extrinsic component of cytoplasmic side of plasma membrane / regulation of heart rate / monoatomic ion transmembrane transport / sarcomere / sarcoplasmic reticulum / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / establishment of localization in cell / calcium-mediated signaling / calcium ion transmembrane transport / sarcolemma / calcium channel activity / response to hydrogen peroxide / Stimuli-sensing channels / Z disc / intracellular calcium ion homeostasis / response to calcium ion / calcium ion transport / : / nuclear envelope / positive regulation of cytosolic calcium ion concentration / protein refolding / scaffold protein binding / transmembrane transporter binding / response to hypoxia / calmodulin binding / signaling receptor binding / calcium ion binding / protein kinase binding / enzyme binding Similarity search - Function | |||||||||||||||||||||
Biological species | Mus musculus (house mouse) / Homo sapiens (human) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.49 Å | |||||||||||||||||||||
Authors | Kobayashi T / Tsutsumi A / Kurebayashi N / Kodama M / Kikkawa M / Murayama T / Ogawa H | |||||||||||||||||||||
Funding support | Japan, 6 items
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Citation | Journal: Nat Commun / Year: 2022 Title: Molecular basis for gating of cardiac ryanodine receptor explains the mechanisms for gain- and loss-of function mutations. Authors: Takuya Kobayashi / Akihisa Tsutsumi / Nagomi Kurebayashi / Kei Saito / Masami Kodama / Takashi Sakurai / Masahide Kikkawa / Takashi Murayama / Haruo Ogawa / Abstract: Cardiac ryanodine receptor (RyR2) is a large Ca release channel in the sarcoplasmic reticulum and indispensable for excitation-contraction coupling in the heart. RyR2 is activated by Ca and RyR2 ...Cardiac ryanodine receptor (RyR2) is a large Ca release channel in the sarcoplasmic reticulum and indispensable for excitation-contraction coupling in the heart. RyR2 is activated by Ca and RyR2 mutations are implicated in severe arrhythmogenic diseases. Yet, the structural basis underlying channel opening and how mutations affect the channel remains unknown. Here, we address the gating mechanism of RyR2 by combining high-resolution structures determined by cryo-electron microscopy with quantitative functional analysis of channels carrying various mutations in specific residues. We demonstrated two fundamental mechanisms for channel gating: interactions close to the channel pore stabilize the channel to prevent hyperactivity and a series of interactions in the surrounding regions is necessary for channel opening upon Ca binding. Mutations at the residues involved in the former and the latter mechanisms cause gain-of-function and loss-of-function, respectively. Our results reveal gating mechanisms of the RyR2 channel and alterations by pathogenic mutations at the atomic level. | |||||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33936.map.gz | 218.8 MB | EMDB map data format | |
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Header (meta data) | emd-33936-v30.xml emd-33936.xml | 15.7 KB 15.7 KB | Display Display | EMDB header |
Images | emd_33936.png | 124.9 KB | ||
Others | emd_33936_half_map_1.map.gz emd_33936_half_map_2.map.gz | 189.9 MB 189.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33936 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33936 | HTTPS FTP |
-Related structure data
Related structure data | 7vmmMC 7vmlC 7vmnC 7vmoC 7vmpC 7vmrC 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 |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_33936.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Structure of recombinant RyR2 (EGTA dataset, class 1, closed state) | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.284 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Structure of recombinant RyR2 (EGTA dataset, class 1, closed state)
File | emd_33936_half_map_1.map | ||||||||||||
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Annotation | Structure of recombinant RyR2 (EGTA dataset, class 1, closed state) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Structure of recombinant RyR2 (EGTA dataset, class 1, closed state)
File | emd_33936_half_map_2.map | ||||||||||||
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Annotation | Structure of recombinant RyR2 (EGTA dataset, class 1, closed state) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Recombinant RyR2 in the presence of EGTA
Entire | Name: Recombinant RyR2 in the presence of EGTA |
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Components |
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-Supramolecule #1: Recombinant RyR2 in the presence of EGTA
Supramolecule | Name: Recombinant RyR2 in the presence of EGTA / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 / Details: in complex with FKBP12.6 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #2: Ryanodine receptor 2
Supramolecule | Name: Ryanodine receptor 2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Supramolecule #3: FKBP1B
Supramolecule | Name: FKBP1B / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Sugar embedding | Material: buffer |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.49 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 45120 |