Structures of the human cholecystokinin receptors bound to agonists and antagonists

doi:10.1038/s41589-021-00866-8

	Structures of the human cholecystokinin receptors bound to agonists and antagonists
	Zhang, Xuefeng 1,2,3; He, Chenglin 4; Wang, Mu1,2,3,5 ; Zhou, Qingtong6,7 ; Yang, Dehua 1,2,3,8; Zhu, Ya 1,2; Feng, Wenbo 4; Zhang, Hui 1,2,3; Dai, Antao 8; Chu, Xiaojing 1,2; Wang, Jia 8; Yang, Zhenlin 1,2; Jiang, Yi 1,2; Sensfuss, Ulrich 9; Tan, Qiuxiang 1,2; Han, Shuo 1,2; Reedtz-Runge, Steffen 9; Xu, H. Eric 1,2,3; Zhao, Suwen5,6 ; Wang, Ming-Wei1,2,3,4,5,7,8 ; Wu, Beili1,2,3,5,10 ; Zhao, Qiang 1,2,3,11,12
	2021-12
发表期刊	NATURE CHEMICAL BIOLOGY (IF:12.9[JCR-2023],14.7[5-Year])
ISSN	1552-4450
EISSN	1552-4469
DOI	10.1038/s41589-021-00866-8
摘要	Cholecystokinin receptors, CCKAR and CCKBR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal structures of the human CCKAR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKBR-gastrin in complex with G(i2) and G(q), respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors.
收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000698565300007
出版者	NATURE PORTFOLIO
原始文献类型	Article; Early Access
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128325
专题	生命科学与技术学院_博士生 iHuman研究所_特聘教授组_Andrej Sali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 iHuman研究所_PI研究组_赵素文组
通讯作者	Zhao, Suwen; Wang, Ming-Wei; Wu, Beili; Zhao, Qiang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Beijing, Peoples R China; 4.Fudan Univ, Sch Pharm, Shanghai, Peoples R China; 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 6.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China; 7.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai, Peoples R China; 8.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai, Peoples R China; 9.Novo Nordisk AS, Malov, Denmark; 10.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China; 11.Chinese Aacademy Sci, Inst Drug Discovery, Zhongshan Inst Drug Discovery, Guangzhou, Guangdong, Peoples R China; 12.Chinese Aacademy Sci, Inst Dev, Zhongshan Inst Drug Discovery, Guangzhou, Guangdong, Peoples R China
通讯作者单位	生命科学与技术学院; iHuman研究所
推荐引用方式 GB/T 7714	Zhang, Xuefeng,He, Chenglin,Wang, Mu,et al. Structures of the human cholecystokinin receptors bound to agonists and antagonists[J]. NATURE CHEMICAL BIOLOGY,2021.
APA	Zhang, Xuefeng.,He, Chenglin.,Wang, Mu.,Zhou, Qingtong.,Yang, Dehua.,...&Zhao, Qiang.(2021).Structures of the human cholecystokinin receptors bound to agonists and antagonists.NATURE CHEMICAL BIOLOGY.
MLA	Zhang, Xuefeng,et al."Structures of the human cholecystokinin receptors bound to agonists and antagonists".NATURE CHEMICAL BIOLOGY (2021).