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Open data
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Basic information
Entry | Database: PDB / ID: 7shf | |||||||||
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Title | Cryo-EM structure of GPR158 coupled to the RGS7-Gbeta5 complex | |||||||||
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![]() | SIGNALING PROTEIN / Receptor / complex | |||||||||
Function / homology | ![]() G protein-coupled glycine receptor activity / Inactivation, recovery and regulation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Prostacyclin signalling through prostacyclin receptor / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK ...G protein-coupled glycine receptor activity / Inactivation, recovery and regulation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Prostacyclin signalling through prostacyclin receptor / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / light adaption / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / dark adaptation / Thromboxane signalling through TP receptor / G-protein gamma-subunit binding / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Ca2+ pathway / G alpha (s) signalling events / G alpha (q) signalling events / Extra-nuclear estrogen signaling / negative regulation of voltage-gated calcium channel activity / G alpha (12/13) signalling events / cell tip / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (i) signalling events / GPER1 signaling / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADP signalling through P2Y purinoceptor 1 / positive regulation of potassium ion transmembrane transport / regulation of G protein-coupled receptor signaling pathway / GTPase activating protein binding / parallel fiber to Purkinje cell synapse / positive regulation of neurotransmitter secretion / G protein-coupled dopamine receptor signaling pathway / negative regulation of G protein-coupled receptor signaling pathway / regulation of synapse organization / G-protein alpha-subunit binding / enzyme activator activity / response to amphetamine / GTPase activator activity / positive regulation of GTPase activity / protein localization to plasma membrane / cell projection / brain development / cognition / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / transmembrane signaling receptor activity / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / myelin sheath / nuclear envelope / presynapse / presynaptic membrane / protein-folding chaperone binding / G alpha (i) signalling events / cell body / postsynaptic membrane / response to ethanol / intracellular signal transduction / neuron projection / G protein-coupled receptor signaling pathway / GTPase activity / synapse / dendrite / protein-containing complex / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
![]() | Patil, D.N. / Singh, S. / Singh, A.K. / Martemyanov, K.A. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure of human GPR158 receptor coupled to the RGS7-Gβ5 signaling complex. Authors: Dipak N Patil / Shikha Singh / Thibaut Laboute / Timothy S Strutzenberg / Xingyu Qiu / Di Wu / Scott J Novick / Carol V Robinson / Patrick R Griffin / John F Hunt / Tina Izard / Appu K Singh ...Authors: Dipak N Patil / Shikha Singh / Thibaut Laboute / Timothy S Strutzenberg / Xingyu Qiu / Di Wu / Scott J Novick / Carol V Robinson / Patrick R Griffin / John F Hunt / Tina Izard / Appu K Singh / Kirill A Martemyanov / ![]() ![]() ![]() Abstract: GPR158 is an orphan G protein–coupled receptor (GPCR) highly expressed in the brain, where it controls synapse formation and function. GPR158 has also been implicated in depression, carcinogenesis, ...GPR158 is an orphan G protein–coupled receptor (GPCR) highly expressed in the brain, where it controls synapse formation and function. GPR158 has also been implicated in depression, carcinogenesis, and cognition. However, the structural organization and signaling mechanisms of GPR158 are largely unknown. We used single-particle cryo–electron microscopy (cryo-EM) to determine the structures of human GPR158 alone and bound to an RGS signaling complex. The structures reveal a homodimeric organization stabilized by a pair of phospholipids and the presence of an extracellular Cache domain, an unusual ligand-binding domain in GPCRs. We further demonstrate the structural basis of GPR158 coupling to RGS7-Gβ5. Together, these results provide insights into the unusual biology of orphan receptors and the formation of GPCR-RGS complexes. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 322 KB | Display | ![]() |
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PDB format | ![]() | 258.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 25126MC ![]() 7sheC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 3 types, 4 molecules CDBA
#1: Protein | Mass: 54761.859 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 38778.602 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 88251.633 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Non-polymers , 3 types, 24 molecules ![](data/chem/img/CLR.gif)
![](data/chem/img/EIJ.gif)
![](data/chem/img/PEE.gif)
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#4: Chemical | ChemComp-CLR / #5: Chemical | ChemComp-EIJ / ( | #6: Chemical | ChemComp-PEE / | |
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-Details
Has ligand of interest | N |
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-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: GPCR complex / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.270 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: OTHER / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: cryoSPARC / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 151954 / Symmetry type: POINT |