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Fenofibrate Recognition and Gq Protein Coupling Mechanisms of the Human Cannabinoid Receptor CB1, Adv Sci, 2 Feb 2024

发布时间:2024年01月31日

Advanced Science, 2 February, 2024, DOI:https://doi.org/10.1002/advs.202306311

Fenofibrate Recognition and Gq 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-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.

文章链接:https://onlinelibrary.wiley.com/doi/10.1002/advs.2023063117

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