[English] 日本語
![](img/lk-miru.gif)
- EMDB-27970: CryoEM structure of miniGq-coupled hM3R in complex with iperoxo (... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | CryoEM structure of miniGq-coupled hM3R in complex with iperoxo (local refinement) | |||||||||
![]() | CryoEM structure of Gq-coupled hM3R in complex with Iperoxo | |||||||||
![]() |
| |||||||||
Function / homology | ![]() regulation of monoatomic ion transmembrane transporter activity / regulation of vascular associated smooth muscle contraction / saliva secretion / Acetylcholine regulates insulin secretion / Muscarinic acetylcholine receptors / 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 / Acetylcholine regulates insulin secretion / Muscarinic acetylcholine receptors / 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 / G protein-coupled acetylcholine receptor signaling pathway / positive regulation of insulin secretion / nervous system development / signaling receptor activity / G alpha (q) signalling events / chemical synaptic transmission / basolateral plasma membrane / postsynaptic membrane / G protein-coupled receptor signaling pathway / synapse / dendrite / endoplasmic reticulum membrane / signal transduction / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.56 Å | |||||||||
![]() | Zhang S / Fay JF / Roth BL | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 80.4 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 17.2 KB 17.2 KB | Display Display | ![]() |
Images | ![]() | 60.1 KB | ||
Masks | ![]() | 91.1 MB | ![]() | |
Others | ![]() ![]() ![]() | 85.2 MB 84.4 MB 84.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 646.2 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 645.8 KB | Display | |
Data in XML | ![]() | 12.6 KB | Display | |
Data in CIF | ![]() | 14.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ea0MC ![]() 8e9wC ![]() 8e9xC ![]() 8e9yC ![]() 8e9zC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | CryoEM structure of Gq-coupled hM3R in complex with Iperoxo | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.88 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: Additional Map
File | emd_27970_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Additional Map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half Map 1
File | emd_27970_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half Map 2
File | emd_27970_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : hM3R
Entire | Name: hM3R |
---|---|
Components |
|
-Supramolecule #1: hM3R
Supramolecule | Name: hM3R / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: Muscarinic acetylcholine receptor M3
Macromolecule | Name: Muscarinic acetylcholine receptor M3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 62.966617 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: AGNFSSPDGT TDDPLGGHTV WQVVFIAFLT GILALVTIIG NILVIVSFKV NKQLKTVNNY FLLSLACADL IIGVISMNLF TTYIIMNRW ALGNLACDLW LAIDYVASNA SVMNLLVISF DRYFSITRPL TYRAKRTTKR AGVMIGLAWV ISFVLWAPAI L FWQYFVGK ...String: AGNFSSPDGT TDDPLGGHTV WQVVFIAFLT GILALVTIIG NILVIVSFKV NKQLKTVNNY FLLSLACADL IIGVISMNLF TTYIIMNRW ALGNLACDLW LAIDYVASNA SVMNLLVISF DRYFSITRPL TYRAKRTTKR AGVMIGLAWV ISFVLWAPAI L FWQYFVGK RTVPPGECFI QFLSEPTITF GTAIAAFYMP VTIMTILYWR IYKETEKRTK ELAGLQASGT EAETENFVHP AK RFALKTR SQITKRKRMS LVKEKKAAQT LSAILLAFII TWTPYNIMVL VNTFCDSCIP KTFWNLGYWL CYINSTVNPV CYA LCNKTF RTTFKMLLLC QCDKKKRRKQ QYQQRQSVIF HKRAPEQALG GSGGGGSGGS SSGGGGSGGG GSGGSSSGGV FTLE DFVGD WEQTAAYNLD QVLEQGGVSS LLQNLAVSVT PIQRIVRSGE NALKIDIHVI IPYEGLSADQ MAQIEEVFKV VYPVD DHHF KVILPYGTLV IDGVTPNMLN YFGRPYEGIA VFDGKKITVT GTLWNGNKII DERLITPDGS MLFRVTINSG GSGGHH HHH HHHHH |
-Macromolecule #2: 4-(4,5-dihydro-1,2-oxazol-3-yloxy)-N,N,N-trimethylbut-2-yn-1-aminium
Macromolecule | Name: 4-(4,5-dihydro-1,2-oxazol-3-yloxy)-N,N,N-trimethylbut-2-yn-1-aminium type: ligand / ID: 2 / Number of copies: 1 / Formula: IXO |
---|---|
Molecular weight | Theoretical: 197.254 Da |
Chemical component information | ![]() ChemComp-IXO: |
-Macromolecule #3: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 3 / Number of copies: 1 / Formula: Y01 |
---|---|
Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE-PROPANE |
-
Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 0.3 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
-
Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.56 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 591814 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |