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

## TL;DR

This study reveals the structure of a human cannabinoid receptor bound to a drug and a Gq protein, offering insights into drug recognition and signaling.

## Contribution

The paper reports the first near-atomic resolution cryo-EM structure of the CB1-Gq complex bound to fenofibrate.

## Key findings

- The CB1-Gq complex structure in fenofibrate-bound form was resolved at near-atomic resolution.
- The study elucidates fenofibrate recognition and Gq protein coupling mechanisms of CB1.
- The findings provide structural insights to aid future drug design targeting CB1.

## 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.

The cryo–EM structure of CB1‐Gq complex, in fenofibrate‐bound form, is resolved to elucidate the ligand selectivity of fenofibrate and Gq coupling mechanism to CB1, providing a structural understanding of ligand recognition and Gq coupling mechanisms of CB1.