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- PDB-8ea0: CryoEM structure of miniGq-coupled hM3R in complex with iperoxo (... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8ea0 | |||||||||
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Title | CryoEM structure of miniGq-coupled hM3R in complex with iperoxo (local refinement) | |||||||||
![]() | Muscarinic acetylcholine receptor M3 | |||||||||
![]() | MEMBRANE PROTEIN / GPCR / IXO / active state / hM3R / Iperoxo | |||||||||
Function / homology | ![]() regulation of monoatomic ion transmembrane transporter activity / regulation of vascular associated smooth muscle contraction / 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 / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / positive regulation of smooth muscle contraction ...regulation of monoatomic ion transmembrane transporter activity / regulation of vascular associated smooth muscle contraction / 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 / 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 / G protein-coupled acetylcholine receptor signaling pathway / signaling receptor activity / nervous system development / G alpha (q) signalling events / basolateral plasma membrane / chemical synaptic transmission / postsynaptic membrane / G protein-coupled receptor signaling pathway / dendrite / synapse / endoplasmic reticulum membrane / signal transduction / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.56 Å | |||||||||
![]() | Zhang, S. / Fay, J.F. / Roth, B.L. | |||||||||
Funding support | ![]()
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![]() | ![]() 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 67.4 KB | Display | ![]() |
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PDB format | ![]() | 47.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 23.1 KB | Display | |
Data in CIF | ![]() | 30.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 27970MC ![]() 8e9wC ![]() 8e9xC ![]() 8e9yC ![]() 8e9zC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 62966.617 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Chemical | ChemComp-IXO / |
#3: Chemical | ChemComp-Y01 / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: hM3R / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2100 nm / Nominal defocus min: 300 nm |
Image recording | Electron dose: 59 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 2858 |
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Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.56 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 591814 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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