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TitleCryo-EM structure of human GPR158 receptor coupled to the RGS7-Gβ5 signaling complex.
Journal, issue, pagesScience, Vol. 375, Issue 6576, Page 86-91, Year 2022
Publish dateJan 7, 2022
AuthorsDipak 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 /
PubMed AbstractGPR158 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.
External linksScience / PubMed:34793198 / PubMed Central
MethodsEM (single particle)
Resolution3.4 Å
Structure data

25125

7she

EMDB-25125, PDB-7she:
Cryo-EM structure of human GPR158
Method: EM (single particle) / Resolution: 3.4 Å

25126

7shf

EMDB-25126, PDB-7shf:
Cryo-EM structure of GPR158 coupled to the RGS7-Gbeta5 complex
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM

ChemComp-EIJ:
(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

ChemComp-CLR:
CHOLESTEROL

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsSIGNALING PROTEIN / Receptor / complex

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