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Structures of the glucocorticoid-bound adhesion receptor GPR97-G(o) complex

文献类型：期刊论文

作者Ping, Yu-Qi2,3,6; Mao, Chunyou4,5,7; Xiao, Peng3; Zhao, Ru-Jia3; Jiang, Yi6; Yang, Zhao3; An, Wen-Tao3; Shen, Dan-Dan4,5,7; Yang, Fan3,8; Zhang, Huibing4,5,7
刊名NATURE
出版日期2021-01-06
页码35
ISSN号0028-0836
DOI10.1038/s41586-020-03083-w
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Zhang, Yan(zhang_yan@zju.edu.cn) ; Sun, Jin-Peng(sunjinpeng@bjmu.edu.cn)
英文摘要Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available(1-3). Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97)(4-6), a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-G(o) complexes bound to the anti-inflammatory drug beclomethasone or the steroid hormone cortisol revealed that glucocorticoids bind to a pocket within the transmembrane domain. The steroidal core of glucocorticoids is packed against the 'toggle switch' residue W-6.53, which senses the binding of a ligand and induces activation of the receptor. Active GPR97 uses a quaternary core and HLY motif to fasten the seven-transmembrane bundle and to mediate G protein coupling. The cytoplasmic side of GPR97 has an open cavity, where all three intracellular loops interact with the G(o) protein, contributing to the high basal activity of GRP97. Palmitoylation at the cytosolic tail of the G(o) protein was found to be essential for efficient engagement with GPR97 but is not observed in other solved GPCR complex structures. Our work provides a structural basis for ligand binding to the seven-transmembrane domain of an adhesion GPCR and subsequent G protein coupling.
WOS关键词PROTEIN-COUPLED RECEPTOR ; VISUALIZATION ; CHIMERA ; DOMAIN ; CELLS
资助项目National Key R&D Program of China[2019YFA0904200] ; National Key R&D Program of China[2019YFA0508800] ; National Key R&D Program of China[2016YFA0501303] ; National Science Fund for Distinguished Young Scholars[81825022] ; National Science Fund for Distinguished Young Scholars[81525005] ; National Natural Science Foundation of China[81825022] ; National Natural Science Foundation of China[81773704] ; National Natural Science Foundation of China[81922071] ; National Natural Science Foundation of China[91953000] ; National Natural Science Foundation of China[31971195] ; National Natural Science Foundation of China[31700692] ; National Natural Science Foundation of China[91939301] ; National Natural Science Foundation of China[31770796] ; National Natural Science Foundation of China[21922702] ; Zhejiang Province National Science Fund for Excellent Young Scholars[LR19H310001] ; National Science Fund for Excellent Young Scholars Grant[81922071] ; National Science Fund for Excellent Young Scholars Grant[81822008] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDB37030103] ; Ministry of Science and Technology (China)[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shandong Provincial Natural Science Foundation[ZR2016CQ07] ; Shandong Provincial Natural Science Foundation[ZR2019ZD40] ; Shandong Key Research and Development Program[GG201709260059] ; Rolling program of ChangJiang Scholars and Innovative Research Team in University Grant[IRT_17R68] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2018ZX09711002] ; Shandong University[2020XGB02]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE RESEARCH
WOS记录号WOS:000605565100007
源URL[http://119.78.100.183/handle/2S10ELR8/295853]  
专题中国科学院上海药物研究所
通讯作者Xu, H. Eric; Zhang, Yan; Sun, Jin-Peng
作者单位1.Zhejiang Univ, Sch Med, MOE Frontier Sci Ctr Brain Res & Brain Machine In, Hangzhou, Peoples R China
2.Peking Univ, Minist Educ, Sch Basic Med Sci, Dept Physiol & Pathophysiol,Key Lab Mol Cardiovas, Beijing, Peoples R China
3.Shandong Univ, Cheeloo Coll Med, Dept Biochem & Mol Biol, Minist Educ,Sch Basic Med Sci,Key Lab Expt Terato, Jinan, Shandong, Peoples R China
4.Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Biophys, Hangzhou, Peoples R China
5.Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Pathol, Hangzhou, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Struct & Funct Drug Targets, CAS Key Lab Receptor Res, Shanghai, Peoples R China
7.Zhejiang Univ, Med Ctr, Zhejiang Lab Syst & Precis Med, Hangzhou, Peoples R China
8.Shandong Univ, Cheeloo Coll Med, Sch Basic Med Sci, Minist Educ,Dept Physiol,Key Lab Expt Teratol, Jinan, Shandong, Peoples R China
9.Beijing Inst Life, Natl Ctr Prot Sci Beijing, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing, Peoples R China
10.Tsinghua Univ, Sch Med, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Ping, Yu-Qi,Mao, Chunyou,Xiao, Peng,et al. Structures of the glucocorticoid-bound adhesion receptor GPR97-G(o) complex[J]. NATURE,2021:35.
APA Ping, Yu-Qi.,Mao, Chunyou.,Xiao, Peng.,Zhao, Ru-Jia.,Jiang, Yi.,...&Sun, Jin-Peng.(2021).Structures of the glucocorticoid-bound adhesion receptor GPR97-G(o) complex.NATURE,35.
MLA Ping, Yu-Qi,et al."Structures of the glucocorticoid-bound adhesion receptor GPR97-G(o) complex".NATURE (2021):35.

入库方式： OAI收割

来源：上海药物研究所

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