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DOI	10.1126/science.aaz5346
	Structural basis of Gs and Gi recognition by the human glucagon receptor
	Qiao A.; Han S.; Li X.; Li Z.; Zhao P.; Dai A.; Chang R.; Tai L.; Tan Q.; Chu X.; Ma L.; Thorsen T.S.; Reedtz-Runge S.; Yang D.; Wang M.-W.; Sexton P.M.; Wootten D.; Sun F.; Zhao Q.; Wu B.
发表日期	2020
ISSN	0036-8075
起始页码	1346
结束页码	1352
卷号	367 期号:6484
英文摘要	Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the Gs 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, Gs or Gi1. These two structures adopt a similar open binding cavity to accommodate Gs and Gi1. The Gs binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect Gi more than Gs 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. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	cyclic AMP glucagon glucagon receptor inhibitory guanine nucleotide binding protein stimulatory guanine nucleotide binding protein glucagon receptor inhibitory guanine nucleotide binding protein protein binding stimulatory guanine nucleotide binding protein chemical binding enzyme activity gene expression mutagenicity protein alpha helix Article binding affinity carboxy terminal sequence conformational transition cryoelectron microscopy human molecular recognition mutagenesis priority journal protein binding protein function protein protein interaction protein structure signal transduction binding site chemistry metabolism molecular model protein conformation ultrastructure Binding Sites Cryoelectron Microscopy Glucagon GTP-Binding Protein alpha Subunits, Gi-Go GTP-Binding Protein alpha Subunits, Gs Humans Models, Molecular Protein Binding Protein Conformation Protein Conformation, alpha-Helical Receptors, Glucagon Signal Transduction
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133610
推荐引用方式 GB/T 7714	Qiao A.,Han S.,Li X.,et al. Structural basis of Gs and Gi recognition by the human glucagon receptor[J]. Science,2020,367(6484).
APA	Qiao A..,Han S..,Li X..,Li Z..,Zhao P..,...&Wu B..(2020).Structural basis of Gs and Gi recognition by the human glucagon receptor.,367(6484).
MLA	Qiao A.,et al."Structural basis of Gs and Gi recognition by the human glucagon receptor".367.6484(2020).