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Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor | |
2021-12 | |
Source Publication | NATURE CHEMICAL BIOLOGY
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ISSN | 1552-4450 |
EISSN | 1552-4469 |
DOI | 10.1038/s41589-021-00841-3 |
Abstract | 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. |
URL | 查看原文 |
Indexed By | SCIE |
Language | 英语 |
WOS Research Area | Biochemistry & Molecular Biology |
WOS Subject | Biochemistry & Molecular Biology |
WOS ID | WOS:000698565300004 |
Publisher | NATURE PORTFOLIO |
Original Document Type | Article; Early Access |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128324 |
Collection | 生命科学与技术学院_特聘教授组_徐华强组 生命科学与技术学院_特聘教授组_王明伟组 生命科学与技术学院_特聘教授组_吴蓓丽组 |
Corresponding Author | Xu, H. Eric; Wang, Ming-Wei; Jiang, Yi |
Affiliation | 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 |
Corresponding Author Affilication | School of Life Science and Technology |
Recommended Citation 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. |
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. |
MLA | Liu, Qiufeng,et al."Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor".NATURE CHEMICAL BIOLOGY (2021). |
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