2. Academic Validation
  3. Structures of the ADGRG2-Gs complex in apo and ligand-bound forms

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

  • Nat Chem Biol. 2022 Aug 18. doi: 10.1038/s41589-022-01084-6.
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 Zhu 7,  Chuan-Xin Zhang 8,  Qing-Tao He 3,  Chao Zhang 3,  Yu-Qi Ping 3,  Ru-Jia Zhao 3,  Chuan-Shun Ma 9,  Chang-Hao Liu 1,  Xiao-Ning Zhang 10,  Dan Jiang 3,  Shaohui Huang 1,  Yue-Tong Xi 3,  Dao-Lai Zhang 9,  Chen-Yang Xue 5,  Bai-Sheng Yang 5,  Jian-Yuan Li 11,  Hao-Cheng Lin 12,  Xu-Hui Zeng 10,  Han Zhao 8,  Wen-Ming Xu 13,  Fan Yi 14,  Zhongmin Liu 15,  Jin-Peng Sun 16 17 18,  Xiao Yu 19
Affiliations

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. [email protected].
  • 15 Department of Biology, Southern University of Science and Technology, Shenzhen, China. [email protected].
  • 16 Department of Clinical Laboratory, The Second Hospital, and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. [email protected].
  • 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. [email protected].
  • 18 Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China. [email protected].
  • 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. [email protected].
  • # 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 Gs 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-Gs 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.

Figures
Products