7EW7

Cryo-EM structure of SEW2871-bound Sphingosine-1-phosphate receptor 1 in complex with Gi protein

7EW7 の概要

• エントリーDOI: 10.2210/pdb7ew7/pdb
• EMDBエントリー: 31349
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: homo sapiens, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 176768.87

構造登録者

Jia, G.W.,Yuan, Y.,Su, Z.M.,Shao, Z.H. (登録日: 2021-05-24, 公開日: 2021-09-29, 最終更新日: 2024-10-30)

主引用文献

Yuan, Y.,Jia, G.,Wu, C.,Wang, W.,Cheng, L.,Li, Q.,Li, Z.,Luo, K.,Yang, S.,Yan, W.,Su, Z.,Shao, Z.
Structures of signaling complexes of lipid receptors S1PR1 and S1PR5 reveal mechanisms of activation and drug recognition.
Cell Res., 31:1263-1274, 2021

PubMed Abstract: Sphingosine-1-phosphate (S1P) is an important bioactive lipid molecule in cell membrane metabolism and binds to G protein-coupled S1P receptors (S1PRs) to regulate embryonic development, physiological homeostasis, and pathogenic processes in various organs. S1PRs are lipid-sensing receptors and are therapeutic targets for drug development, including potential treatment of COVID-19. Herein, we present five cryo-electron microscopy structures of S1PRs bound to diverse drug agonists and the heterotrimeric Gi protein. Our structural and functional assays demonstrate the different binding modes of chemically distinct agonists of S1PRs, reveal the mechanical switch that activates these receptors, and provide a framework for understanding ligand selectivity and G protein coupling.

PubMed: 34526663
DOI: 10.1038/s41422-021-00566-x

実験手法

ELECTRON MICROSCOPY (3.27 Å)