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Yorodumi- PDB-6x33: Wt pig RyR1 in complex with apoCaM, EGTA condition (class 3, open) -
+Open data
-Basic information
Entry | Database: PDB / ID: 6x33 | ||||||
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Title | Wt pig RyR1 in complex with apoCaM, EGTA condition (class 3, open) | ||||||
Components |
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Keywords | TRANSPORT PROTEIN/ISOMERASE/CALCIUM BINDING PROTEIN / receptor / calcium / channel / complex / TRANSPORT PROTEIN-ISOMERASE-CALCIUM BINDING PROTEIN complex | ||||||
Function / homology | Function and homology information positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of release of sequestered calcium ion into cytosol / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers ...positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of release of sequestered calcium ion into cytosol / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / 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 / Loss of phosphorylation of MECP2 at T308 / 'de novo' protein folding / 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) / positive regulation of cyclic-nucleotide phosphodiesterase activity / organelle localization by membrane tethering / negative regulation of heart rate / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / regulation of cardiac muscle cell action potential / Activation of RAC1 downstream of NMDARs / 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 / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / Phase 0 - rapid depolarisation / negative regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / channel regulator activity / RHO GTPases activate PAKs / : / 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 / regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / response to vitamin E / cellular response to interferon-beta / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / calcium channel inhibitor activity / Protein methylation / eNOS activation / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Activation of AMPK downstream of NMDARs / T cell proliferation / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / release of sequestered calcium ion into cytosol / : / Ion homeostasis / titin binding / regulation of calcium-mediated signaling / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / sperm midpiece / regulation of cytosolic calcium ion concentration / sarcoplasmic reticulum membrane / calcium channel complex / substantia nigra development / adenylate cyclase activator activity / Ras activation upon Ca2+ influx through NMDA receptor / regulation of heart rate / sarcomere / FCERI mediated Ca+2 mobilization / protein serine/threonine kinase activator activity / FCGR3A-mediated IL10 synthesis / VEGFR2 mediated vascular permeability / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / VEGFR2 mediated cell proliferation / regulation of cytokinesis / positive regulation of peptidyl-threonine phosphorylation / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / Translocation of SLC2A4 (GLUT4) to the plasma membrane / spindle microtubule / RAF activation / calcium-mediated signaling / positive regulation of receptor signaling pathway via JAK-STAT Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Sus scrofa (pig) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 Å | ||||||
Authors | Woll, K.W. / Haji-Ghassemi, O. / Van Petegem, F. | ||||||
Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2021 Title: Pathological conformations of disease mutant Ryanodine Receptors revealed by cryo-EM. Authors: Kellie A Woll / Omid Haji-Ghassemi / Filip Van Petegem / Abstract: Ryanodine Receptors (RyRs) are massive channels that release Ca from the endoplasmic and sarcoplasmic reticulum. Hundreds of mutations are linked to malignant hyperthermia (MH), myopathies, and ...Ryanodine Receptors (RyRs) are massive channels that release Ca from the endoplasmic and sarcoplasmic reticulum. Hundreds of mutations are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, we explore the first MH mutation identified in humans by providing cryo-EM snapshots of the pig homolog, R615C, showing that it affects an interface between three solenoid regions. We also show the impact of apo-calmodulin (apoCaM) and how it can induce opening by bending of the bridging solenoid, mediated by its N-terminal lobe. For R615C RyR1, apoCaM binding abolishes a pathological 'intermediate' conformation, distributing the population to a mixture of open and closed channels, both different from the structure without apoCaM. Comparisons show that the mutation primarily affects the closed state, inducing partial movements linked to channel activation. This shows that disease mutations can cause distinct pathological conformations of the RyR and facilitate channel opening by disrupting interactions between different solenoid regions. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6x33.cif.gz | 2.5 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6x33.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6x33.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6x33_validation.pdf.gz | 1002.9 KB | Display | wwPDB validaton report |
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Full document | 6x33_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 6x33_validation.xml.gz | 336.1 KB | Display | |
Data in CIF | 6x33_validation.cif.gz | 535.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x3/6x33 ftp://data.pdbj.org/pub/pdb/validation_reports/x3/6x33 | HTTPS FTP |
-Related structure data
Related structure data | 22016MC 6w1nC 6x32C 6x34C 6x35C 6x36C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 11667.305 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FKBP1B, FKBP12.6, FKBP1L, FKBP9, OTK4 / Production host: Escherichia coli (E. coli) / References: UniProt: P68106, peptidylprolyl isomerase #2: Protein | Mass: 425092.250 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) #3: Protein | Mass: 16723.365 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CALM1, CALM, CAM, CAM1 / Production host: Escherichia coli (E. coli) / References: UniProt: P0DP23 #4: Chemical | ChemComp-ZN / Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: DIFFRACTION |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
-Processing
EM software | Name: PHENIX / Version: dev-3714 / Category: 3D reconstruction |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 25122 / Symmetry type: POINT |