Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor
文献类型:期刊论文
作者 | Liu, Qiufeng1; Yang, Dehua1,2,3; Zhuang, Youwen1; Croll, Tristan I.4; Cai, Xiaoqing3; Dai, Antao3; He, Xinheng1,2; Duan, Jia1,2; Yin, Wanchao1; Ye, Chenyu5 |
刊名 | NATURE CHEMICAL BIOLOGY |
出版日期 | 2021-09-23 |
卷号 | 17期号:12页码:1238-1244 |
关键词 | a Receptor Structural Basis Binding-site Cck1 Receptor Agonist Activation Mechanism Optimization Discovery Rat |
DOI | 10.1038/s41589-021-00841-3 |
文献子类 | Article |
英文摘要 |
Cholecystokinin A receptor (CCKAR) belongs to family A G-protein-coupled receptors and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKAR is its ability to interact with a sulfated ligand and to couple with divergent G-protein subtypes, including G(s), G(i) and G(q). However, the basis for G-protein coupling promiscuity and ligand recognition by CCKAR remains unknown. Here, we present three cryo-electron microscopy structures of sulfated CCK-8-activated CCKAR in complex with G(s), G(i) and G(q) heterotrimers, respectively. CCKAR presents a similar conformation in the three structures, whereas conformational differences in the 'wavy hook' of the G alpha subunits and ICL3 of the receptor serve as determinants in G-protein coupling selectivity. Our findings provide a framework for understanding G-protein coupling promiscuity by CCKAR and uncover the mechanism of receptor recognition by sulfated CCK-8. |
语种 | 英语 |
WOS记录号 | WOS:000698565300004 |
源URL | [http://119.78.100.183/handle/2S10ELR8/309441] |
专题 | 新药研究国家重点实验室 |
通讯作者 | Xu, H. Eric; Wang, Ming-Wei; Jiang, Yi |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai, Peoples R China 4.Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge, England 5.Fudan Univ, Sch Pharm, Shanghai, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 7.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Beijing, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 9.Fudan Univ, Sch Basic Med Sci, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Liu, Qiufeng,Yang, Dehua,Zhuang, Youwen,et al. Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor[J]. NATURE CHEMICAL BIOLOGY,2021,17(12):1238-1244. |
APA | Liu, Qiufeng.,Yang, Dehua.,Zhuang, Youwen.,Croll, Tristan I..,Cai, Xiaoqing.,...&Jiang, Yi.(2021).Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor.NATURE CHEMICAL BIOLOGY,17(12),1238-1244. |
MLA | Liu, Qiufeng,et al."Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor".NATURE CHEMICAL BIOLOGY 17.12(2021):1238-1244. |
入库方式: OAI收割
来源:上海药物研究所
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