Beschreibung:
<jats:title>Abstract</jats:title><jats:p>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<jats:sub>i</jats:sub> complexes in synthetic agonist‐bound forms have been resolved to date. However, the commercial drug recognition and G<jats:sub>q</jats:sub> coupling mechanisms of CB1 remain elusive. Herein, the cryo‐electron microscopy (cryo‐EM) structure of CB1‐G<jats:sub>q</jats:sub> complex, in fenofibrate‐bound form, at near‐atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and G<jats:sub>q</jats:sub> protein coupling by CB1 and will facilitate future drug discovery and design.</jats:p>