PDF(Pubmed)
Abstract：
The G-protein-coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1-Gi complexes in synthetic agonist-bound forms have been resolved to date. However, the commercial drug recognition and Gq coupling mechanisms of CB1 remain elusive. Herein, the cryo-electron microscopy (cryo-EM) structure of CB1-Gq complex, in fenofibrate-bound form, at near-atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and Gq protein coupling by CB1 and will facilitate future drug discovery and design.
摘要：
G蛋白偶联的人类大麻素受体1（CB1）是疼痛管理的一个有前途的治疗目标，炎症,肥胖，和药物滥用障碍。迄今为止,合成的激动剂结合形式的CB1-Gi复合物的结构已经被解析。然而,CB1的商业药物识别和Gq偶联机制仍然难以捉摸。在这里，CB1-Gq复合物的低温电子显微镜（cryo-EM）结构，非诺贝特结合形式，在近原子分辨率下，据报道。该结构阐明了CB1精确识别非诺贝特和Gq蛋白偶联的微妙机制，并将促进未来的药物发现和设计。
