DataVXAdvanced SciencePaper
journal article·2024-04Open access

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

Advanced Science· Volume 11· Issue 14
Publisher pageOpen full text
Source abstract

Abstract

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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Protein Structure and Dynamics · Mass Spectrometry Techniques and Applications · Receptor Mechanisms and Signaling

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

CAS Key Laboratory of Quantitative Engineering Biology Institute of Synthetic Biology Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China

iHuman Institute ShanghaiTech University 393 Middle Huaxia Road Pudong Shanghai 201210 China

Institute of Biophysics Chinese Academy of Sciences 15 Datun Road Chaoyang District Beijing 100101 China

School of Life Sciences University of Chinese Academy of Sciences Beijing 100049 China

Key Laboratory of Biomacromolecules Chinese Academy of Sciences Beijing 100101 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

References (41)

Show source-provided references
1. 10.1073/pnas.87.5.193210.1073/pnas.87.5.1932 ↗
2. 10.1016/j.tips.2020.06.01010.1016/j.tips.2020.06.010 ↗
3. 10.1126/science.147091910.1126/science.1470919 ↗
4. 10.1016/0006-2952(95)00109-D10.1016/0006-2952(95)00109-D ↗
5. 10.1080/10408444.2020.176253910.1080/10408444.2020.1762539 ↗
6. Howlett A. C. · Mol. Pharmacol. · 1985 · 27 · 42910.1016/S0026-895X(25)12377-8 ↗
7. 10.1073/pnas.050958810210.1073/pnas.0509588102 ↗
8. 10.1124/pr.110.00300410.1124/pr.110.003004 ↗
9. 10.2165/00003495-200767010-0001310.2165/00003495-200767010-00013 ↗
10. 10.1111/bph.1366810.1111/bph.13668 ↗
11. 10.1016/j.pnpbp.2014.02.00910.1016/j.pnpbp.2014.02.009 ↗
12. 10.1096/fj.14-26305310.1096/fj.14-263053 ↗
13. 10.1016/j.cell.2016.10.00410.1016/j.cell.2016.10.004 ↗
14. 10.1038/nature2061310.1038/nature20613 ↗
15. 10.1038/nature2327210.1038/nature23272 ↗
16. 10.1016/j.cell.2018.11.04010.1016/j.cell.2018.11.040 ↗
17. 10.1038/s41589-019-0387-210.1038/s41589-019-0387-2 ↗
18. 10.1038/s41467-023-37864-410.1038/s41467-023-37864-4 ↗
19. 10.1016/j.cell.2020.01.00810.1016/j.cell.2020.01.008 ↗
20. 10.1038/s41467-020-17933-810.1038/s41467-020-17933-8 ↗
21. 10.1371/journal.pone.017564210.1371/journal.pone.0175642 ↗
22. 10.1038/nature1036110.1038/nature10361 ↗
23. Ballesteros J. A. · 1995 · 366
24. 10.1021/jacs.1c0684710.1021/jacs.1c06847 ↗
25. 10.1038/s41422-021-00591-w10.1038/s41422-021-00591-w ↗
26. 10.1126/science.aaz534610.1126/science.aaz5346 ↗
27. 10.1016/j.cell.2020.03.00310.1016/j.cell.2020.03.003 ↗
28. 10.1042/BCJ2021070810.1042/BCJ20210708 ↗
29. 10.1038/nmeth.419310.1038/nmeth.4193 ↗
30. 10.1038/nmeth.416910.1038/nmeth.4169 ↗
31. 10.1107/S205979831700006710.1107/S2059798317000067 ↗
32. 10.1002/pro.394310.1002/pro.3943 ↗
33. 10.1107/S090744491000749310.1107/S0907444910007493 ↗
34. 10.1107/S205979831901147110.1107/S2059798319011471 ↗
35. 10.1002/pro.333010.1002/pro.3330 ↗
36. 10.1002/jcc.2370210.1002/jcc.23702 ↗
37. 10.1021/acs.jctc.5b0093510.1021/acs.jctc.5b00935 ↗
38. 10.1016/j.jmgm.2005.12.00510.1016/j.jmgm.2005.12.005 ↗
39. 10.1016/j.softx.2015.06.00110.1016/j.softx.2015.06.001 ↗
40. 10.1063/1.47011710.1063/1.470117 ↗
41. 10.1016/j.bpj.2015.08.01510.1016/j.bpj.2015.08.015 ↗