7SHE

Cryo-EM structure of human GPR158

Summary for 7SHE

• Entry DOI: 10.2210/pdb7she/pdb
• EMDB information: 25125 25126
• Descriptor: G-protein coupled receptor 158, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, (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, ... (4 entities in total)
• Functional Keywords: receptor, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 186640.82

Authors

Patil, D.N.,Singh, S.,Singh, A.K.,Martemyanov, K.A. (deposition date: 2021-10-08, release date: 2021-12-01, Last modification date: 2022-01-19)

Primary citation

Patil, D.N.,Singh, S.,Laboute, T.,Strutzenberg, T.S.,Qiu, X.,Wu, D.,Novick, S.J.,Robinson, C.V.,Griffin, P.R.,Hunt, J.F.,Izard, T.,Singh, A.K.,Martemyanov, K.A.
Cryo-EM structure of human GPR158 receptor coupled to the RGS7-G beta 5 signaling complex.
Science, 375:86-91, 2022

PubMed 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, 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.

PubMed: 34793198
DOI: 10.1126/science.abl4732

Experimental method

ELECTRON MICROSCOPY (3.4 Å)