Fenofibrate Recognition and Gq Protein Coupling Mechanisms of the Human Cannabinoid Receptor CB1
ADVANCED SCIENCE(2024)
摘要
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.
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关键词
cryo-electron microscopy,fenofibrate,G(q) coupling,human cannabinoid receptor 1,ligand recognition
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