+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25125 | |||||||||
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Title | Cryo-EM structure of human GPR158 | |||||||||
Map data | ||||||||||
Sample |
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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 | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Patil DN / Singh S / Singh AK / Martemyanov KA | |||||||||
Funding support | United States, 1 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_25125.map.gz | 228 MB | EMDB map data format | |
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Header (meta data) | emd-25125-v30.xml emd-25125.xml | 13.4 KB 13.4 KB | Display Display | EMDB header |
Images | emd_25125.png | 56.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25125 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25125 | HTTPS FTP |
-Validation report
Summary document | emd_25125_validation.pdf.gz | 442.5 KB | Display | EMDB validaton report |
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Full document | emd_25125_full_validation.pdf.gz | 442.1 KB | Display | |
Data in XML | emd_25125_validation.xml.gz | 7.2 KB | Display | |
Data in CIF | emd_25125_validation.cif.gz | 8.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25125 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25125 | HTTPS FTP |
-Related structure data
Related structure data | 7sheMC 7shfC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_25125.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.873 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Receptor
Entire | Name: Receptor |
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Components |
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-Supramolecule #1: Receptor
Supramolecule | Name: Receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 170 KDa |
-Macromolecule #1: G-protein coupled receptor 158
Macromolecule | Name: G-protein coupled receptor 158 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 88.251633 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGAMAYPLLL CLLLAQLGLG AVGASRDPQG RPDSPRERTP KGKPHAQQPG RASASDSSAP WSRSTDGTIL AQKLAEEVPM DVASYLYTG DSHQLKRANC SGRYELAGLP GKWPALASAH PSLHRALDTL THATNFLNVM LQSNKSREQN LQDDLDWYQA L VWSLLEGE ...String: MGAMAYPLLL CLLLAQLGLG AVGASRDPQG RPDSPRERTP KGKPHAQQPG RASASDSSAP WSRSTDGTIL AQKLAEEVPM DVASYLYTG DSHQLKRANC SGRYELAGLP GKWPALASAH PSLHRALDTL THATNFLNVM LQSNKSREQN LQDDLDWYQA L VWSLLEGE PSISRAAITF STDSLSAPAP QVFLQATREE SRILLQDLSS SAPHLANATL ETEWFHGLRR KWRPHLHRRG PN QGPRGLG HSWRRKDGLG GDKSHFKWSP PYLECENGSY KPGWLVTLSS AIYGLQPNLV PEFRGVMKVD INLQKVDIDQ CSS DGWFSG THKCHLNNSE CMPIKGLGFV LGAYECICKA GFYHPGVLPV NNFRRRGPDQ HISGSTKDVS EEAYVCLPCR EGCP FCADD SPCFVQEDKY LRLAIISFQA LCMLLDFVSM LVVYHFRKAK SIRASGLILL ETILFGSLLL YFPVVILYFE PSTFR CILL RWARLLGFAT VYGTVTLKLH RVLKVFLSRT AQRIPYMTGG RVMRMLAVIL LVVFWFLIGW TSSVCQNLEK QISLIG QGK TSDHLIFNMC LIDRWDYMTA VAEFLFLLWG VYLCYAVRTV PSAFHEPRYM AVAVHNELII SAIFHTIRFV LASRLQS DW MLMLYFAHTH LTVTVTIGLL LIPKFSHSSN NPRDDIATEA YEDELDMGRS GSYLNSSINS AWSEHSLDPE DIRDELKK L YAQLEIYKRK KMITNNPHLQ KKRCSKKGLG RSIMRRITEI PETVSRQCSK EDKELEVLFQ |
-Macromolecule #2: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
Macromolecule | Name: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / type: ligand / ID: 2 / Number of copies: 1 / Formula: PEE |
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Molecular weight | Theoretical: 744.034 Da |
Chemical component information | ChemComp-PEE: |
-Macromolecule #3: (2S)-1-{[(S)-hydroxy{[(1s,2R,3R,4R,5S,6S)-2,3,4,5,6-pentahydroxyc...
Macromolecule | Name: (2S)-1-{[(S)-hydroxy{[(1s,2R,3R,4R,5S,6S)-2,3,4,5,6-pentahydroxycyclohexyl]oxy}phosphoryl]oxy}-3-(octadecanoyloxy)propan-2-yl (5E,8E,11E,14E)-icosa-5,8,11,14-tetraenoate type: ligand / ID: 3 / Number of copies: 1 / Formula: EIJ |
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Molecular weight | Theoretical: 887.128 Da |
Chemical component information | ChemComp-EIJ: |
-Macromolecule #4: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 4 / Number of copies: 22 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.3 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-7she: |