Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor

doi:10.1038/s41589-021-00841-3

	Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor
	Liu, Qiufeng 1; Yang, Dehua 1,2,3; Zhuang, Youwen 1; Croll, Tristan I.4; Cai, Xiaoqing 3; Dai, Antao 3; He, Xinheng 1,2; Duan, Jia 1,2; Yin, Wanchao 1; Ye, Chenyu 5; Zhou, Fulai 1; Wu, Beili1,2,6,7 ; Zhao, Qiang 2,7,8; Xu, H. Eric1,2,6 ; Wang, Ming-Wei1,2,3,5,6,9 ; Jiang, Yi 1,2
	2021-12
Source Publication	NATURE CHEMICAL BIOLOGY
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.
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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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