+Open data
-Basic information
Entry | Database: PDB / ID: 7she | |||||||||
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Title | Cryo-EM structure of human GPR158 | |||||||||
Components | G-protein coupled receptor 158 | |||||||||
Keywords | SIGNALING PROTEIN / Receptor | |||||||||
Function / homology | Function and homology information G protein-coupled glycine receptor activity / regulation of G protein-coupled receptor signaling pathway / positive regulation of neurotransmitter secretion / regulation of synapse organization / enzyme activator activity / cognition / cell projection / protein localization to plasma membrane / brain development / transmembrane signaling receptor activity ...G protein-coupled glycine receptor activity / regulation of G protein-coupled receptor signaling pathway / positive regulation of neurotransmitter secretion / regulation of synapse organization / enzyme activator activity / cognition / cell projection / protein localization to plasma membrane / brain development / transmembrane signaling receptor activity / presynaptic membrane / postsynaptic membrane / G protein-coupled receptor signaling pathway / nucleus / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Patil, D.N. / Singh, S. / Singh, A.K. / Martemyanov, K.A. | |||||||||
Funding support | United States, 1items
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Citation | Journal: Science / Year: 2022 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 |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7she.cif.gz | 211.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7she.ent.gz | 176.2 KB | Display | PDB format |
PDBx/mmJSON format | 7she.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7she_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 7she_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 7she_validation.xml.gz | 47.3 KB | Display | |
Data in CIF | 7she_validation.cif.gz | 65.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sh/7she ftp://data.pdbj.org/pub/pdb/validation_reports/sh/7she | HTTPS FTP |
-Related structure data
Related structure data | 25125MC 7shfC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 88251.633 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GPR158, KIAA1136 / Production host: Homo sapiens (human) / References: UniProt: Q5T848 #2: Chemical | ChemComp-PEE / | #3: Chemical | ChemComp-EIJ / ( | #4: Chemical | ChemComp-CLR / Has ligand of interest | Y | |
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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 |
-Sample preparation
Component | Name: Receptor / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.170 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Conc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
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) |
-Processing
EM software | Name: cryoSPARC / Version: 3.1 / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Particle selection | Num. of particles selected: 4374550 |
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 263237 / Symmetry type: POINT |
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |