+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30067 | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of RyR1 (Ca2+/Caffeine/ATP/CaM1234/CHL) | |||||||||||||||
Map data | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL | |||||||||||||||
Sample |
| |||||||||||||||
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 release of sequestered calcium ion into cytosol / terminal cisterna / negative regulation of insulin secretion involved in cellular response to glucose stimulus / ryanodine receptor complex / 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 release of sequestered calcium ion into cytosol / terminal cisterna / negative regulation of insulin secretion involved in cellular response to glucose stimulus / ryanodine receptor complex / 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 / ossification involved in bone maturation / Sodium/Calcium exchangers / cell communication by electrical coupling involved in cardiac conduction / response to redox state / Calmodulin induced events / protein maturation by protein folding / Reduction of cytosolic Ca++ levels / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / skin development / 'de novo' protein folding / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / negative regulation of heart rate / PKA activation / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / negative regulation of calcium ion export across plasma membrane / organelle localization by membrane tethering / Activation of RAC1 downstream of NMDARs / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / CLEC7A (Dectin-1) induces NFAT activation / autophagosome membrane docking / negative regulation of phosphoprotein phosphatase activity / FK506 binding / positive regulation of axon regeneration / positive regulation of ryanodine-sensitive calcium-release channel activity / Negative regulation of NMDA receptor-mediated neuronal transmission / regulation of cell communication by electrical coupling involved in cardiac conduction / Unblocking of NMDA receptors, glutamate binding and activation / negative regulation of peptidyl-threonine phosphorylation / cellular response to caffeine / Synthesis of IP3 and IP4 in the cytosol / intracellularly gated calcium channel activity / outflow tract morphogenesis / Phase 0 - rapid depolarisation / protein phosphatase activator activity / RHO GTPases activate PAKs / positive regulation of cyclic-nucleotide phosphodiesterase activity / positive regulation of phosphoprotein phosphatase activity / Long-term potentiation / Ion transport by P-type ATPases / organelle membrane / Uptake and function of anthrax toxins / : / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / catalytic complex / DARPP-32 events / detection of calcium ion / toxic substance binding / smooth muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / voltage-gated calcium channel activity / RHO GTPases activate IQGAPs / response to vitamin E / regulation of cardiac muscle contraction / calcium channel inhibitor activity / cellular response to interferon-beta / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / skeletal muscle fiber development / protein peptidyl-prolyl isomerization / voltage-gated potassium channel complex / Activation of AMPK downstream of NMDARs / T cell proliferation / eNOS activation / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / regulation of calcium-mediated signaling / release of sequestered calcium ion into cytosol / positive regulation of protein dephosphorylation / titin binding / regulation of ryanodine-sensitive calcium-release channel activity / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / Ion homeostasis / positive regulation of protein autophosphorylation / sperm midpiece / sarcoplasmic reticulum membrane / calcium channel complex / regulation of cytosolic calcium ion concentration / substantia nigra development / cellular response to calcium ion / adenylate cyclase activator activity / Ras activation upon Ca2+ influx through NMDA receptor 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
| |||||||||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
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 | |
---|---|---|---|---|
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 |
-Related structure data
Related structure data | 6m2wMC 7cf9C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
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) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Additional map: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified
File | emd_30067_additional.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified
File | emd_30067_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map
File | emd_30067_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map
File | emd_30067_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map | ||||||||||||
Projections & Slices |
| ||||||||||||
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 |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |