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Yorodumi- EMDB-27969: CryoEM structure of miniGq-coupled hM3R in complex with Iperoxo -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27969 | |||||||||
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Title | CryoEM structure of miniGq-coupled hM3R in complex with Iperoxo | |||||||||
Map data | CryoEM structure of miniGq-coupled hM3R in complex with Iperoxo | |||||||||
Sample |
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Function / homology | Function and homology information regulation of monoatomic ion transmembrane transporter activity / saliva secretion / Muscarinic acetylcholine receptors / Acetylcholine regulates insulin secretion / ion channel modulating, G protein-coupled receptor signaling pathway / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / regulation of smooth muscle contraction / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / positive regulation of smooth muscle contraction ...regulation of monoatomic ion transmembrane transporter activity / saliva secretion / Muscarinic acetylcholine receptors / Acetylcholine regulates insulin secretion / ion channel modulating, G protein-coupled receptor signaling pathway / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / regulation of smooth muscle contraction / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / positive regulation of smooth muscle contraction / phosphatidylinositol phospholipase C activity / G protein-coupled serotonin receptor activity / acetylcholine binding / acetylcholine receptor signaling pathway / ligand-gated ion channel signaling pathway / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / smooth muscle contraction / basal plasma membrane / calcium-mediated signaling / protein modification process / positive regulation of insulin secretion / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / signaling receptor activity / nervous system development / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / basolateral plasma membrane / G alpha (q) signalling events / chemical synaptic transmission / postsynaptic membrane / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / dendrite / synapse / endoplasmic reticulum membrane / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.69 Å | |||||||||
Authors | Zhang S / Fay JF / Roth BL | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nature / Year: 2022 Title: Molecular basis for selective activation of DREADD-based chemogenetics. Authors: Shicheng Zhang / Ryan H Gumpper / Xi-Ping Huang / Yongfeng Liu / Brian E Krumm / Can Cao / Jonathan F Fay / Bryan L Roth / Abstract: Designer receptors exclusively activated by designer drugs (DREADDs) represent a powerful chemogenetic technology for the remote control of neuronal activity and cellular signalling. The muscarinic ...Designer receptors exclusively activated by designer drugs (DREADDs) represent a powerful chemogenetic technology for the remote control of neuronal activity and cellular signalling. The muscarinic receptor-based DREADDs are the most widely used chemogenetic tools in neuroscience research. The G-coupled DREADD (hM3Dq) is used to enhance neuronal activity, whereas the G-coupled DREADD (hM4Di) is utilized to inhibit neuronal activity. Here we report four DREADD-related cryogenic electron microscopy high-resolution structures: a hM3Dq-miniG complex and a hM4Di-miniG complex bound to deschloroclozapine; a hM3Dq-miniG complex bound to clozapine-N-oxide; and a hM3R-miniG complex bound to iperoxo. Complemented with mutagenesis, functional and computational simulation data, our structures reveal key details of the recognition of DREADD chemogenetic actuators and the molecular basis for activation. These findings should accelerate the structure-guided discovery of next-generation chemogenetic tools. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27969.map.gz | 77.7 MB | EMDB map data format | |
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Header (meta data) | emd-27969-v30.xml emd-27969.xml | 21.3 KB 21.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27969_fsc.xml | 13.3 KB | Display | FSC data file |
Images | emd_27969.png | 61.4 KB | ||
Others | emd_27969_half_map_1.map.gz emd_27969_half_map_2.map.gz | 84.5 MB 84.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27969 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27969 | HTTPS FTP |
-Validation report
Summary document | emd_27969_validation.pdf.gz | 631.9 KB | Display | EMDB validaton report |
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Full document | emd_27969_full_validation.pdf.gz | 631.5 KB | Display | |
Data in XML | emd_27969_validation.xml.gz | 18.7 KB | Display | |
Data in CIF | emd_27969_validation.cif.gz | 24.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27969 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27969 | HTTPS FTP |
-Related structure data
Related structure data | 8e9zMC 8e9wC 8e9xC 8e9yC 8ea0C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_27969.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | CryoEM structure of miniGq-coupled hM3R in complex with Iperoxo | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.88 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half Map 1
File | emd_27969_half_map_1.map | ||||||||||||
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Annotation | Half Map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map 2
File | emd_27969_half_map_2.map | ||||||||||||
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Annotation | Half Map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Gq-coupled hM3R complex
+Supramolecule #1: Gq-coupled hM3R complex
+Supramolecule #2: muscarinic acetylcholine receptor 3, miniGq protein, Guanine nucl...
+Supramolecule #3: Single-chain variable fragment scFv16
+Macromolecule #1: Muscarinic acetylcholine receptor M3
+Macromolecule #2: miniGq
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: scFv16
+Macromolecule #6: 4-(4,5-dihydro-1,2-oxazol-3-yloxy)-N,N,N-trimethylbut-2-yn-1-aminium
+Macromolecule #7: CHOLESTEROL HEMISUCCINATE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 2858 / Average electron dose: 59.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 0.2 µm |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |