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Open data
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Basic information
Entry | Database: PDB / ID: 6m2w | |||||||||||||||
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Title | Structure of RyR1 (Ca2+/Caffeine/ATP/CaM1234/CHL) | |||||||||||||||
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![]() | MEMBRANE PROTEIN / Rabbit / Ryanodine receptor1 / CHL. | |||||||||||||||
Function / homology | ![]() 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 / ryanodine receptor complex / negative regulation of release of sequestered calcium ion into cytosol / 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 / ryanodine receptor complex / 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 / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / ossification involved in bone maturation / 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 / 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 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 / organelle membrane / 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 / 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 / Phase 0 - rapid depolarisation / outflow tract morphogenesis / negative regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / channel regulator activity / intracellularly gated calcium channel 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 / toxic substance binding / Smooth Muscle Contraction / smooth endoplasmic reticulum / response to vitamin E / voltage-gated calcium channel activity / 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 / skeletal muscle fiber development / striated muscle contraction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / muscle contraction / 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 / cellular response to calcium ion / adenylate cyclase activator activity Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||||||||
![]() | Ma, R. / Haji-Ghassemi, O. / Ma, D. / Lin, L. / Samurkas, A. / Van Petegem, F. / Yuchi, Z. | |||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() 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. | |||||||||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 2.7 MB | Display | ![]() |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 30067MC ![]() 7cf9C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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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) ![]() ![]() #2: Protein | Mass: 11667.305 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #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.) ![]() ![]() ![]() |
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-Non-polymers , 5 types, 20 molecules ![](data/chem/img/CFF.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/ATP.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/F0U.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/ATP.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/F0U.gif)
#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 |