Structural highlights
Function
[GP158_HUMAN] Orphan receptor.
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.
References
- ↑ 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
