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Yorodumi- EMDB-33938: Structure of recombinant RyR2 (Ca2+ dataset, class 1, open state) -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33938 | |||||||||||||||||||||
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Title | Structure of recombinant RyR2 (Ca2+ dataset, class 1, open state) | |||||||||||||||||||||
Map data | Structure of recombinant RyR2 (Ca2 dataset, class 1, open 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 / 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 / calcium ion transmembrane import into cytosol / response to caffeine / A band / 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 / 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 / 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 / smooth endoplasmic reticulum / negative regulation of ryanodine-sensitive calcium-release channel activity / response to vitamin E / 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 / Ion homeostasis / regulation of ryanodine-sensitive calcium-release channel activity / monoatomic ion transmembrane transport / extrinsic component of cytoplasmic side of plasma membrane / sarcoplasmic reticulum membrane / calcium channel complex / cellular response to epinephrine stimulus / regulation of cytosolic calcium ion concentration / response to muscle stretch / regulation of heart rate / sarcomere / peptidylprolyl isomerase / sarcoplasmic reticulum / peptidyl-prolyl cis-trans isomerase activity / establishment of localization in cell / calcium-mediated signaling / calcium ion transmembrane transport / calcium channel activity / response to hydrogen peroxide / Stimuli-sensing channels / sarcolemma / 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 / calmodulin binding / response to hypoxia / signaling receptor binding / calcium ion binding / protein kinase binding / enzyme binding / protein-containing complex / identical protein binding / membrane Similarity search - Function | |||||||||||||||||||||
Biological species | Mus musculus (house mouse) / Homo sapiens (human) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.45 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_33938.map.gz | 139.3 MB | EMDB map data format | |
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Header (meta data) | emd-33938-v30.xml emd-33938.xml | 15.8 KB 15.8 KB | Display Display | EMDB header |
Images | emd_33938.png | 126.9 KB | ||
Others | emd_33938_half_map_1.map.gz emd_33938_half_map_2.map.gz | 113.1 MB 113.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33938 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33938 | HTTPS FTP |
-Validation report
Summary document | emd_33938_validation.pdf.gz | 899.6 KB | Display | EMDB validaton report |
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Full document | emd_33938_full_validation.pdf.gz | 899.2 KB | Display | |
Data in XML | emd_33938_validation.xml.gz | 14.1 KB | Display | |
Data in CIF | emd_33938_validation.cif.gz | 16.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33938 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33938 | HTTPS FTP |
-Related structure data
Related structure data | 7vmoMC 7vmlC 7vmmC 7vmnC 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_33938.map.gz / Format: CCP4 / Size: 149.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Structure of recombinant RyR2 (Ca2 dataset, class 1, open state) | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.239 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 (Ca2 dataset, class 1, open state)
File | emd_33938_half_map_1.map | ||||||||||||
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Annotation | Structure of recombinant RyR2 (Ca2 dataset, class 1, open state) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Structure of recombinant RyR2 (Ca2 dataset, class 1, open state)
File | emd_33938_half_map_2.map | ||||||||||||
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Annotation | Structure of recombinant RyR2 (Ca2 dataset, class 1, open state) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Recombinant RyR2 in the presence of Ca2+
Entire | Name: Recombinant RyR2 in the presence of Ca2+ |
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Components |
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-Supramolecule #1: Recombinant RyR2 in the presence of Ca2+
Supramolecule | Name: Recombinant RyR2 in the presence of Ca2+ / 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) / Recombinant cell: HEK293 |
-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: Peptidyl-prolyl cis-trans isomerase FKBP1B
Supramolecule | Name: Peptidyl-prolyl cis-trans isomerase 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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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm |
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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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.45 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 45432 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |