+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30067 | |||||||||||||||
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Title | Structure of RyR1 (Ca2+/Caffeine/ATP/CaM1234/CHL) | |||||||||||||||
Map data | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL | |||||||||||||||
Sample |
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Keywords | Rabbit / Ryanodine receptor1 / CHL. / MEMBRANE PROTEIN | |||||||||||||||
Function / homology | Function and homology information ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / 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 ...ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / 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 / cell communication by electrical coupling involved in cardiac conduction / 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 / negative regulation of heart rate / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / negative regulation of phosphoprotein phosphatase activity / 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 / intracellularly gated calcium channel activity / protein phosphatase activator activity / RHO GTPases activate PAKs / : / organelle membrane / positive regulation of phosphoprotein phosphatase activity / 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 / toxic substance binding / smooth endoplasmic reticulum / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / response to vitamin E / voltage-gated calcium channel activity / calcium channel inhibitor activity / cellular response to interferon-beta / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / eNOS activation / skeletal muscle fiber development / protein peptidyl-prolyl isomerization / striated muscle contraction / T cell proliferation / Activation of AMPK downstream of NMDARs / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / release of sequestered calcium ion into cytosol / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / positive regulation of protein dephosphorylation / Ion homeostasis / regulation of calcium-mediated signaling / regulation of ryanodine-sensitive calcium-release channel activity / titin binding / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / sperm midpiece / sarcoplasmic reticulum membrane / calcium channel complex / muscle contraction / regulation of cytosolic calcium ion concentration / cellular response to calcium ion Similarity search - Function | |||||||||||||||
Biological species | Oryctolagus cuniculus (rabbit) / Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||||||||
Authors | Ma R / Haji-Ghassemi O | |||||||||||||||
Funding support | China, Canada, 4 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_30067.map.gz | 33.4 MB | EMDB map data format | |
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Header (meta data) | emd-30067-v30.xml emd-30067.xml | 31.1 KB 31.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_30067_fsc.xml | 15.9 KB | Display | FSC data file |
Images | emd_30067.png | 336.2 KB | ||
Filedesc metadata | emd-30067.cif.gz | 9.1 KB | ||
Others | emd_30067_additional.map.gz emd_30067_additional_1.map.gz emd_30067_half_map_1.map.gz emd_30067_half_map_2.map.gz | 79.2 MB 79.2 MB 267.8 MB 267.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30067 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30067 | HTTPS FTP |
-Validation report
Summary document | emd_30067_validation.pdf.gz | 851.4 KB | Display | EMDB validaton report |
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Full document | emd_30067_full_validation.pdf.gz | 850.9 KB | Display | |
Data in XML | emd_30067_validation.xml.gz | 23.5 KB | Display | |
Data in CIF | emd_30067_validation.cif.gz | 31 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30067 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30067 | HTTPS FTP |
-Related structure data
Related structure data | 6m2wMC 7cf9C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_30067.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified
File | emd_30067_additional.map | ||||||||||||
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Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified
File | emd_30067_additional_1.map | ||||||||||||
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Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map
File | emd_30067_half_map_1.map | ||||||||||||
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Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map
File | emd_30067_half_map_2.map | ||||||||||||
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Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : RyR1 Ca2 /ATP/caffeine/CaM1234/CHL
+Supramolecule #1: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL
+Supramolecule #2: RyR1
+Supramolecule #3: FKBP12.6 and CAM1234
+Macromolecule #1: Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ry...
+Macromolecule #2: Peptidyl-prolyl cis-trans isomerase FKBP1B
+Macromolecule #3: Calmodulin-1
+Macromolecule #4: CAFFEINE
+Macromolecule #5: CALCIUM ION
+Macromolecule #6: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #7: ZINC ION
+Macromolecule #8: 5-bromanyl-N-[4-chloranyl-2-methyl-6-(methylcarbamoyl)phenyl]-2-(...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |