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  2. 上海药物研究所
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  4. 新药研究国家重点实验室
Structures of the human cholecystokinin receptors bound to agonists and antagonists

文献类型：期刊论文

作者Zhang, Xuefeng1,2,3; He, Chenglin4; Wang, Mu1,2,3,5; Zhou, Qingtong6,7; Yang, Dehua1,2,3,8; Zhu, Ya1,2; Feng, Wenbo4; Zhang, Hui1,2,3; Dai, Antao8; Chu, Xiaojing1,2
刊名NATURE CHEMICAL BIOLOGY
出版日期2021-12
卷号17期号:12页码:1230-1237
ISSN号1552-4450
DOI10.1038/s41589-021-00866-8
文献子类Article
英文摘要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.
WOS关键词SUBTYPE SELECTIVITY ; BIOLOGICAL-ACTIVITY ; FORCE-FIELD ; GASTRIN ; CCK ; BINDING ; POTENT ; MECHANISM ; AFFINITY ; GROMACS
WOS研究方向Biochemistry & Molecular Biology
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:000698565300007
源URL[http://119.78.100.183/handle/2S10ELR8/309367]  
专题新药研究国家重点实验室
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;
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,2021,17(12):1230-1237.
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,17(12),1230-1237.
MLA Zhang, Xuefeng,et al."Structures of the human cholecystokinin receptors bound to agonists and antagonists".NATURE CHEMICAL BIOLOGY 17.12(2021):1230-1237.

入库方式： OAI收割

来源：上海药物研究所

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