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

作者：Lin, Hui; Xiao, Peng; Bu, Rui-Qian; Guo, Shengchao; Yang, Zhao; Yuan, Daopeng; Zhu, Zhong-Liang; Zhang, Chuan-Xin; He, Qing-Tao; Zhang, Chao; Ping, Yu-Qi; Zhao, Ru-Jia; Ma, Chuan-Shun; Liu, Chang-Hao; Zhang, Xiao-Ning; Jiang, Dan; Huang, Shaohui; Xi, Yue-Tong; Zhang, Dao-Lai; Xue, Chen-Yang; Yang, Bai-Sheng; Li, Jian-Yuan; Lin, Hao-Cheng; Zeng, Xu-Hui; Zhao, Han; Xu, Wen-Ming; Yi, Fan^*; Liu, Zhongmin^*; Sun, Jin-Peng^*; Yu, Xiao^*

来源：Nature Chemical Biology, 2022, 18(11): 1196-+.

DOI：10.1038/s41589-022-01084-6

• PROTEIN-COUPLED RECEPTORS
• CRYO-EM STRUCTURE
• AGONIST
• GENE
• MUTATIONS
• PREDICTS
• PEPTIDE
• VARIANT
• HE6

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.

• 单位
  北京大学第三医院; 北京大学; 国家卫生计生委科学技术研究所; 中国科学技术大学; 南通大学; 山东大学; 清华大学; 滨州医学院; 四川大学