Structures of the ADGRG2-G_s complex in apo and ligand-bound forms

Hui Lin^#^{1

2

3

4}, Peng Xiao^#^{2

3}, Rui-Qian Bu^#⁵, Shengchao Guo^#³, Zhao Yang^#^{1

3}, Daopeng Yuan^#⁶, Zhong-Liang Zhu⁷, Chuan-Xin Zhang⁸, Qing-Tao He³, Chao Zhang³, Yu-Qi Ping³, Ru-Jia Zhao³, Chuan-Shun Ma⁹, Chang-Hao Liu¹, Xiao-Ning Zhang¹⁰, Dan Jiang³, Shaohui Huang¹, Yue-Tong Xi³, Dao-Lai Zhang⁹, Chen-Yang Xue⁵, Bai-Sheng Yang⁵, Jian-Yuan Li¹¹, Hao-Cheng Lin¹², Xu-Hui Zeng¹⁰, Han Zhao⁸, Wen-Ming Xu¹³, Fan Yi¹⁴, Zhongmin Liu¹⁵, Jin-Peng Sun^{16

17

18}, Xiao Yu¹⁹

Affiliations

¹ Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Clinical Laboratory, The Second Hospital, and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
³ Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ Key Laboratory of Molecular Cardiovascular Science of the Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.
⁵ Department of Biology, Southern University of Science and Technology, Shenzhen, China.
⁶ School of Medicine, Tsinghua University, Beijing, China.
⁷ School of Life Sciences, University of Science and Technology of China, Hefei, China.
⁸ Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁹ School of Pharmacy, Binzhou Medical University, Yantai, China.
¹⁰ Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, China.
¹¹ Key Laboratory of Male Reproductive Health, National Research Institute for Family Planning, National Health and Family Planning Commission, Beijing, China.
¹² Department of Urology, Peking University Third Hospital, Beijing, China.
¹³ Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
¹⁴ Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China. fanyi@sdu.edu.cn.
¹⁵ Department of Biology, Southern University of Science and Technology, Shenzhen, China. liuzm@sustech.edu.cn.
¹⁶ Department of Clinical Laboratory, The Second Hospital, and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. sunjinpeng@bjmu.edu.cn.
¹⁷ Key Laboratory of Molecular Cardiovascular Science of the Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China. sunjinpeng@bjmu.edu.cn.
¹⁸ Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China. sunjinpeng@bjmu.edu.cn.
¹⁹ Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China. yuxiao@sdu.edu.cn.

^# Contributed equally.

PMID: 35982227
DOI: 10.1038/s41589-022-01084-6

Structures of the ADGRG2-G_s complex in apo and ligand-bound forms

Hui Lin et al. Nat Chem Biol. 2022 Nov.

. 2022 Nov;18(11):1196-1203.

doi: 10.1038/s41589-022-01084-6. Epub 2022 Aug 18.

Authors

Affiliations

¹ Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Clinical Laboratory, The Second Hospital, and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
³ Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ Key Laboratory of Molecular Cardiovascular Science of the Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.
⁵ Department of Biology, Southern University of Science and Technology, Shenzhen, China.
⁶ School of Medicine, Tsinghua University, Beijing, China.
⁷ School of Life Sciences, University of Science and Technology of China, Hefei, China.
⁸ Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁹ School of Pharmacy, Binzhou Medical University, Yantai, China.
¹⁰ Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, China.
¹¹ Key Laboratory of Male Reproductive Health, National Research Institute for Family Planning, National Health and Family Planning Commission, Beijing, China.
¹² Department of Urology, Peking University Third Hospital, Beijing, China.
¹³ Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
¹⁴ Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China. fanyi@sdu.edu.cn.
¹⁵ Department of Biology, Southern University of Science and Technology, Shenzhen, China. liuzm@sustech.edu.cn.
¹⁶ Department of Clinical Laboratory, The Second Hospital, and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. sunjinpeng@bjmu.edu.cn.
¹⁷ Key Laboratory of Molecular Cardiovascular Science of the Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China. sunjinpeng@bjmu.edu.cn.
¹⁸ Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China. sunjinpeng@bjmu.edu.cn.
¹⁹ Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China. yuxiao@sdu.edu.cn.

^# Contributed equally.

PMID: 35982227
DOI: 10.1038/s41589-022-01084-6

Abstract

Adhesion G protein-coupled receptors are elusive in terms of their structural information and ligands. Here, we solved the cryogenic-electron microscopy (cryo-EM) structure of apo-ADGRG2, an essential membrane receptor for maintaining male fertility, in complex with a G_s trimer. Whereas the formations of two kinks were determinants of the active state, identification of a potential ligand-binding pocket in ADGRG2 facilitated the screening and identification of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate and deoxycorticosterone as potential ligands of ADGRG2. The cryo-EM structures of DHEA-ADGRG2-G_s provided interaction details for DHEA within the seven transmembrane domains of ADGRG2. Collectively, our data provide a structural basis for the activation and signaling of ADGRG2, as well as characterization of steroid hormones as ADGRG2 ligands, which might be used as useful tools for further functional studies of the orphan ADGRG2.

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References

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Structures of the ADGRG2-G_s complex in apo and ligand-bound forms

Affiliations

Structures of the ADGRG2-G_s complex in apo and ligand-bound forms

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases