7ewr

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Cryo-EM structure of human GPR158 in complex with RGS7-Gbeta5 in a 2:2:2 ratio

Structural highlights

7ewr is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 4.7Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RGS7_HUMAN Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(o)-alpha is specifically enhanced by the RGS6/GNG5 dimer. May play a role in synaptic vesicle exocytosis. May play important role in the rapid regulation of neuronal excitability and the cellular responses to short-lived stimulations (By similarity).

Publication Abstract from PubMed

GPR158, a class C orphan GPCR, functions in cognition, stress-induced mood control, and synaptic development. Among class C GPCRs, GPR158 is unique as it lacks a Venus flytrap-fold ligand-binding domain and terminates Galphai/o protein signaling through the RGS7-Gbeta5 heterodimer. Here, we report the cryo-EM structures of GPR158 alone and in complex with one or two RGS7-Gbeta5 heterodimers. GPR158 dimerizes through Per-Arnt-Sim-fold extracellular and transmembrane (TM) domains connected by an epidermal growth factor-like linker. The TM domain (TMD) reflects both inactive and active states of other class C GPCRs: a compact intracellular TMD, conformations of the two intracellular loops (ICLs) and the TMD interface formed by TM4/5. The ICL2, ICL3, TM3, and first helix of the cytoplasmic coiled-coil provide a platform for the DHEX domain of one RGS7 and the second helix recruits another RGS7. The unique features of the RGS7-binding site underlie the selectivity of GPR158 for RGS7.

Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gbeta5.,Jeong E, Kim Y, Jeong J, Cho Y Nat Commun. 2021 Nov 23;12(1):6805. doi: 10.1038/s41467-021-27147-1. PMID:34815401[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
5 reviews cite this structure
Research Status of the Orphan G Protein Coupled Receptor 158 and Future Perspectives.
Fu et al. (2022)
4 more
7 other articles
No citations found

See Also

References

  1. ↑ Jeong E, Kim Y, Jeong J, Cho Y. Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gbeta5. Nat Commun. 2021 Nov 23;12(1):6805. doi: 10.1038/s41467-021-27147-1. PMID:34815401 doi:http://dx.doi.org/10.1038/s41467-021-27147-1

Contents


PDB ID 7ewr

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OCA

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