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

doi:10.1126/science.aaz5346

	Structural basis of G(s) and G(i) recognition by the human glucagon receptor
	Qiao, Anna 1,2,3; Han, Shuo 1,2; Li, Xinmei 3,4; Li, Zhixin 5; Zhao, Peishen 6,7; Dai, Antao 1,8; Chang, Rulve 5; Tai, Linhua 3,4; Tan, Qiuxiang 1,2; Chu, Xiaojing 1,2
刊名	SCIENCE
	2020-03-20
卷号	367 期号:6484 页码:1346-+
ISSN号	0036-8075
DOI	10.1126/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.
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关键词	CRYO-EM STRUCTURE ; GLP-1 RECEPTOR ; SPECIFICITY ; ACTIVATION ; COMPLEX ; CELLS ; CA2+
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS记录号	WOS:000522167400046
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280867]
专题	中国科学院上海药物研究所
通讯作者	Wootten, Denise; Sun, Fei; Zhao, Qiang; Wu, Beili
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Natl Lab Biomacromol, Natl Ctr Prot Sci Beijing, CAS Ctr Excellence Biomacromol,Inst Biophys, Beijing 100101, Peoples R China 5.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China 6.Monash Univ, Drug Discovery Biol, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia 7.Monash Univ, Dept Pharmacol, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia 8.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 9.Novo Nordisk AS, DK-2760 Malov, Denmark 10.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, 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-+.