Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor
2021-12
Source PublicationNATURE CHEMICAL BIOLOGY
ISSN1552-4450
EISSN1552-4469
DOI10.1038/s41589-021-00841-3
AbstractCholecystokinin 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.
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Indexed BySCIE
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000698565300004
PublisherNATURE PORTFOLIO
Original Document TypeArticle; Early Access
Citation statistics
Document Type期刊论文
Identifierhttps://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 AuthorXu, 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 AffilicationSchool 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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