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Structural basis of G(s) and G(i) recognition by the human glucagon receptor

文献类型：期刊论文

作者Qiao, Anna3,4,5; Han, Shuo3,4; Li, Xinmei5,6; Li, Zhixin7; Zhao, Peishen8,9; Dai, Antao3,10; Chang, Rulve7; Tai, Linhua5,6; Tan, Qiuxiang3,4; Chu, Xiaojing3,4
刊名SCIENCE
出版日期2020-03-20
卷号367期号:6484页码:1346-+
ISSN号0036-8075
DOI10.1126/science.aaz5346
通讯作者Wootten, Denise(denise.wootten@monash.edu) ; Sun, Fei(feisun@ibp.ac.cn) ; Zhao, Qiang(zhaoq@simm.ac.cn) ; Wu, Beili(beiliwu@simm.ac.cn)
英文摘要Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G(s) class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo-electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, G(s) or G(i1). These two structures adopt a similar open binding cavity to accommodate G(s) and G(i1). The G(s) binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect G(i) more than G(s) binding. Conformational differences in the receptor intracellular loops were found to be key selectivity determinants. These distinctions in transducer engagement were supported by mutagenesis and functional studies.
WOS关键词CRYO-EM STRUCTURE ; GLP-1 RECEPTOR ; SPECIFICITY ; ACTIVATION ; COMPLEX ; CELLS ; CA2+
资助项目National Key R&D Program of China[2018YFA0507000] ; National Key R&D Program of China[2017YFA0504703] ; National Science Foundation of China[31825010] ; National Science Foundation of China[81525024] ; National Science Foundation of China[31830020] ; National Science Foundation of China[81872915] ; National Science Foundation of China[81773792] ; CAS Strategic Priority Research Program[XDB37000000] ; Shanghai Outstanding Academic Leaders Plan of Shanghai Municipal Science and Technology Committee[18XD1404800] ; National Science & Technology Major Project-Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; Shanghai Science and Technology Development Fund[16ZR1407100] ; Australian National Health and Medical Research Council (NHMRC)[1126857] ; Australian National Health and Medical Research Council (NHMRC)[1150083] ; National Mega R&D Program for Drug Discovery[2018ZX09735-001]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000522167400046
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/280867]  
专题新药研究国家重点实验室
通讯作者Wootten, Denise; Sun, Fei; Zhao, Qiang; Wu, Beili
作者单位1.Chinese Acad Sci, Ctr Biol Imaging, Inst Biophys, Beijing 100101, Peoples R China
2.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Beijing 100101, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Natl Lab Biomacromol, Natl Ctr Prot Sci Beijing, CAS Ctr Excellence Biomacromol,Inst Biophys, Beijing 100101, Peoples R China
7.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
8.Monash Univ, Drug Discovery Biol, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia
9.Monash Univ, Dept Pharmacol, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia
10.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Qiao, Anna,Han, Shuo,Li, Xinmei,et al. Structural basis of G(s) and G(i) recognition by the human glucagon receptor[J]. SCIENCE,2020,367(6484):1346-+.
APA Qiao, Anna.,Han, Shuo.,Li, Xinmei.,Li, Zhixin.,Zhao, Peishen.,...&Wu, Beili.(2020).Structural basis of G(s) and G(i) recognition by the human glucagon receptor.SCIENCE,367(6484),1346-+.
MLA Qiao, Anna,et al."Structural basis of G(s) and G(i) recognition by the human glucagon receptor".SCIENCE 367.6484(2020):1346-+.

入库方式： OAI收割

来源：上海药物研究所

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