Structures of the ADGRG2-Gs complex in apo and ligand-bound forms
Structures of the ADGRG2-Gs complex in apo and ligand-bound forms
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DOI：
10.1038/s41589-022-01084-6
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发表时间：
2022-08-18
影响因子：
14.8
通讯作者：
Yu, Xiao
中科院分区：
文献类型：
--
作者：
Lin, Hui;Xiao, Peng;Yu, Xiao
粘附G蛋白偶联受体在结构信息和配体方面是难以捉摸的。在这里，我们解决了低温电镜（cryo-EM）结构的apo-ADGRG2，一个重要的膜受体维持男性的生育能力，与G(s)三聚体复合物。虽然两个扭结的形成是活性状态的决定因素，但在ADGRG2中发现一个潜在的配体结合口袋，有助于筛选和鉴定脱氢表雄酮（DHEA）、硫酸脱氢表雄酮和脱氧皮质酮作为ADGRG2的潜在配体。DHEA-ADGRG2- g (s)的低温电镜结构提供了DHEA在ADGRG2的七个跨膜结构域中相互作用的细节。总的来说，我们的数据为ADGRG2的激活和信号传导提供了结构基础，以及类固醇激素作为ADGRG2配体的表征，这可能被用作孤儿ADGRG2进一步功能研究的有用工具。
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.