7EWR

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

Summary for 7EWR

• Entry DOI: 10.2210/pdb7ewr/pdb
• Related: 7EWL 7EWP
• EMDB information: 31351 31360 31363 31363 31365 31366
• Descriptor: Regulator of G-protein signaling 7, Guanine nucleotide-binding protein subunit beta-5, Probable G-protein coupled receptor 158 (3 entities in total)
• Functional Keywords: gpcr, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 465472.98

Authors

Kim, Y.,Jeong, E.,Jeong, J.,Cho, Y. (deposition date: 2021-05-26, release date: 2021-12-01, Last modification date: 2024-11-20)

Primary citation

Jeong, E.,Kim, Y.,Jeong, J.,Cho, Y.
Structure of the class C orphan GPCR GPR158 in complex with RGS7-G beta 5.
Nat Commun, 12:6805-6805, 2021

PubMed Abstract: 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 Gαi/o protein signaling through the RGS7-Gβ5 heterodimer. Here, we report the cryo-EM structures of GPR158 alone and in complex with one or two RGS7-Gβ5 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.

PubMed: 34815401
DOI: 10.1038/s41467-021-27147-1

Experimental method

ELECTRON MICROSCOPY (4.7 Å)