+Open data
-Basic information
Entry | Database: PDB / ID: 6m2w | |||||||||||||||
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Title | Structure of RyR1 (Ca2+/Caffeine/ATP/CaM1234/CHL) | |||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Rabbit / Ryanodine receptor1 / CHL. | |||||||||||||||
Function / homology | Function and homology information ATP-gated ion channel activity / 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 / terminal cisterna / negative regulation of release of sequestered calcium ion into cytosol / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation ...ATP-gated ion channel activity / 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 / terminal cisterna / negative regulation of release of sequestered calcium ion into cytosol / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / CaM pathway / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Cam-PDE 1 activation / Sodium/Calcium exchangers / Reduction of cytosolic Ca++ levels / Calmodulin induced events / ossification involved in bone maturation / response to redox state / protein maturation by protein folding / 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 / organelle localization by membrane tethering / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / skin development / negative regulation of heart rate / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / regulation of cardiac muscle cell action potential / FK506 binding / organelle membrane / 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 / Synthesis of IP3 and IP4 in the cytosol / negative regulation of peptidyl-threonine phosphorylation / Negative regulation of NMDA receptor-mediated neuronal transmission / cellular response to caffeine / Phase 0 - rapid depolarisation / Unblocking of NMDA receptors, glutamate binding and activation / negative regulation of ryanodine-sensitive calcium-release channel activity / adenylate cyclase activator activity / protein phosphatase activator activity / channel regulator activity / outflow tract morphogenesis / RHO GTPases activate PAKs / Ion transport by P-type ATPases / intracellularly gated calcium channel activity / : / Uptake and function of anthrax toxins / Long-term potentiation / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / DARPP-32 events / regulation of cardiac muscle contraction / detection of calcium ion / smooth muscle contraction / Smooth Muscle Contraction / response to vitamin E / regulation of ryanodine-sensitive calcium-release channel activity / toxic substance binding / cellular response to interferon-beta / voltage-gated calcium channel activity / smooth endoplasmic reticulum / RHO GTPases activate IQGAPs / calcium channel inhibitor activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / eNOS activation / Protein methylation / voltage-gated potassium channel complex / skeletal muscle fiber development / T cell proliferation / striated muscle contraction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Activation of AMPK downstream of NMDARs / Ion homeostasis / muscle contraction / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / : / titin binding / release of sequestered calcium ion into cytosol / positive regulation of protein autophosphorylation / regulation of calcium-mediated signaling / sperm midpiece / regulation of cytosolic calcium ion concentration / sarcoplasmic reticulum membrane / calcium channel complex / substantia nigra development / Ras activation upon Ca2+ influx through NMDA receptor Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) Oryctolagus cuniculus (rabbit) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||||||||
Authors | Ma, R. / Haji-Ghassemi, O. / Ma, D. / Lin, L. / Samurkas, A. / Van Petegem, F. / Yuchi, Z. | |||||||||||||||
Funding support | China, Canada, 4items
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Citation | Journal: Nat Chem Biol / Year: 2020 Title: Structural basis for diamide modulation of ryanodine receptor. Authors: Ruifang Ma / Omid Haji-Ghassemi / Dan Ma / Heng Jiang / Lianyun Lin / Li Yao / Arthur Samurkas / Yuxin Li / Yiwen Wang / Peng Cao / Shian Wu / Yan Zhang / Takashi Murayama / Bernard Moussian ...Authors: Ruifang Ma / Omid Haji-Ghassemi / Dan Ma / Heng Jiang / Lianyun Lin / Li Yao / Arthur Samurkas / Yuxin Li / Yiwen Wang / Peng Cao / Shian Wu / Yan Zhang / Takashi Murayama / Bernard Moussian / Filip Van Petegem / Zhiguang Yuchi / Abstract: The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the ...The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the highest-resolution cryo-electron microscopy (cryo-EM) structure of RyR1 in the open state, in complex with the anthranilic diamide chlorantraniliprole (CHL). The 3.2-Å local resolution map facilitates unambiguous assignment of the CHL binding site. The molecule induces a conformational change by affecting the S4-S5 linker, triggering channel opening. The binding site is further corroborated by mutagenesis data, which reveal how diamide insecticides are selective to the Lepidoptera group of insects over honeybee or mammalian RyRs. Our data reveal that several pests have developed resistance via two mechanisms, steric hindrance and loss of contact. Our results provide a foundation for the development of highly selective pesticides aimed at overcoming resistance and therapeutic molecules to treat human myopathies. | |||||||||||||||
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 | 6m2w.cif.gz | 2.7 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6m2w.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6m2w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6m2w_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 6m2w_full_validation.pdf.gz | 2 MB | Display | |
Data in XML | 6m2w_validation.xml.gz | 377 KB | Display | |
Data in CIF | 6m2w_validation.cif.gz | 598.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m2/6m2w ftp://data.pdbj.org/pub/pdb/validation_reports/m2/6m2w | HTTPS FTP |
-Related structure data
Related structure data | 30067MC 7cf9C 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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1 |
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-Components
-Protein , 3 types, 12 molecules ADGJBEHKCFIL
#1: Protein | Mass: 539851.000 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: P11716 #2: 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 #3: Protein | Mass: 16620.402 Da / Num. of mol.: 4 / Mutation: E32A, E68A, E105A, E141A 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 |
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-Non-polymers , 5 types, 20 molecules
#4: Chemical | ChemComp-CFF / #5: Chemical | ChemComp-CA / #6: Chemical | ChemComp-ATP / #7: Chemical | ChemComp-ZN / #8: Chemical | ChemComp-F0U / |
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-Details
Has ligand of interest | Y |
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Sequence details | Complete sequence of RyR1 protein is: ...Complete sequence of RyR1 protein is: MGDGGEGEDE |