Advanced Science, 31 January, 2024, DOI：https://doi.org/10.1002/advs.202306311

Fenofibrate Recognition and G_q Protein Coupling Mechanisms of the Human Cannabinoid Receptor CB1

Tianxin Wang, Wenqin Tang, Ziyi Zhao, Ran Zhao, Zhenyu Lv, Xuzhen Guo, Quanchang Gu, Boxiang Liu, Haoyu Lv, Jiayan Chen, Kaiquan Zhang, Fahui Li, Jiangyun Wang

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-G_i complexes in synthetic agonist-bound forms have been resolved to date. However, the commercial drug recognition and G_q coupling mechanisms of CB1 remain elusive. Herein, the cryo-electron microscopy (cryo-EM) structure of CB1-G_q complex, in fenofibrate-bound form, at near-atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and G_q protein coupling by CB1 and will facilitate future drug discovery and design.

Article link：https://onlinelibrary.wiley.com/doi/10.1002/advs.202306311