近日，美国匹兹堡大学Xiang-Qun Xie、Cheng Zhang和中国科学院上海药物所徐华强等研究人合作解析了人类大麻素受体CB2-Gi信号复合物的冷冻电镜结构。这一研究成果于2020年1月30日在线发表在国际学术期刊《细胞》上。
Title: Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex
Author: Changrui Xing, Youwen Zhuang, Ting-Hai Xu, Zhiwei Feng, X. Edward Zhou, Maozi Chen, Lei Wang, Xing Meng, Ying Xue, Junmei Wang, Heng Liu, Terence Francis McGuire, Gongpu Zhao, Karsten Melcher, Cheng Zhang, H. Eric Xu, Xiang-Qun Xie
Issue&Volume: January 30, 2020
Abstract: Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders,inflammation, and pain while avoiding psychotropic side effects mediated by CB1. Themechanisms underlying CB2 activation and signaling are poorly understood but criticalfor drug design. Here we report the cryo-EM structure of the human CB2-Gi signaling complex bound to the agonist WIN 55,212-2. The 3D structure reveals thebinding mode of WIN 55,212-2 and structural determinants for distinguishing CB2 agonistsfrom antagonists, which are supported by a pair of rationally designed agonist andantagonist. Further structural analyses with computational docking results uncoverthe differences between CB2 and CB1 in receptor activation, ligand recognition, andGi coupling. These findings are expected to facilitate rational structure-based discoveryof drugs targeting the cannabinoid system.