6PT0

Cryo-EM structure of human cannabinoid receptor 2-Gi protein in complex with agonist WIN 55,212-2

6PT0 の概要

• エントリーDOI: 10.2210/pdb6pt0/pdb
• EMDBエントリー: 20470
• 分子名称: Cannabinoid receptor 2, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (8 entities in total)
• 機能のキーワード: gpcr complex, win55, 212-2, 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: 158678.19

構造登録者

Xu, T.H.,Xing, C.,Zhuang, Y.,Feng, Z.,Zhou, X.E.,Chen, M.,Wang, L.,Meng, X.,Xue, Y.,Wang, J.,Liu, H.,McGuire, T.,Zhao, G.,Melcher, K.,Zhang, C.,Xu, H.E.,Xie, X.Q. (登録日: 2019-07-14, 公開日: 2020-02-12, 最終更新日: 2025-05-28)

主引用文献

Xing, C.,Zhuang, Y.,Xu, T.H.,Feng, Z.,Zhou, X.E.,Chen, M.,Wang, L.,Meng, X.,Xue, Y.,Wang, J.,Liu, H.,McGuire, T.F.,Zhao, G.,Melcher, K.,Zhang, C.,Xu, H.E.,Xie, X.Q.
Cryo-EM Structure of the Human Cannabinoid Receptor CB2-GiSignaling Complex.
Cell, 180:645-, 2020

PubMed Abstract: Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the human CB2-G signaling complex bound to the agonist WIN 55,212-2. The 3D structure reveals the binding mode of WIN 55,212-2 and structural determinants for distinguishing CB2 agonists from antagonists, which are supported by a pair of rationally designed agonist and antagonist. Further structural analyses with computational docking results uncover the differences between CB2 and CB1 in receptor activation, ligand recognition, and G coupling. These findings are expected to facilitate rational structure-based discovery of drugs targeting the cannabinoid system.

PubMed: 32004460
DOI: 10.1016/j.cell.2020.01.007

実験手法

ELECTRON MICROSCOPY (3.2 Å)