7SHE

Cryo-EM structure of human GPR158

7SHE の概要

• エントリーDOI: 10.2210/pdb7she/pdb
• EMDBエントリー: 25125 25126
• 分子名称: 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)
• 機能のキーワード: receptor, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 186640.82

構造登録者

Patil, D.N.,Singh, S.,Singh, A.K.,Martemyanov, K.A. (登録日: 2021-10-08, 公開日: 2021-12-01, 最終更新日: 2022-01-19)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.4 Å)