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

Adv Sci (Weinh). 2024 Jan 31:e2306311. doi: 10.1002/advs.202306311. Online ahead of print.

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.

PMID:38298116 | DOI:10.1002/advs.202306311