A complex structure of arrestin-2 bound to a G protein-coupled receptor

doi:10.1038/s41422-019-0256-2

	A complex structure of arrestin-2 bound to a G protein-coupled receptor
	Yin, Wanchao 2; Li, Zhihai 2,3; Jin, Mingliang 4; Yin, Yu-Ling 2,5; de Waal, Parker W.6; Pal, Kuntal 6,7; Yin, Yanting 2,6; Gao, Xiang 6; He, Yuanzheng 6,8; Gao, Jing 2
刊名	CELL RESEARCH
	2019-12-01
卷号	29 期号:12 页码:971-983
ISSN号	1001-0602
DOI	10.1038/s41422-019-0256-2
通讯作者	Cong, Yao(cong@sibcb.ac.cn) ; Zhou, X. Edward(Edward.Zhou@vai.org) ; Yu, Xuekui(xkyu@simm.ac.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn)
英文摘要	Arrestins comprise a family of signal regulators of G-protein-coupled receptors (GPCRs), which include arrestins 1 to 4. While arrestins 1 and 4 are visual arrestins dedicated to rhodopsin, arrestins 2 and 3 (Arr2 and Arr3) are beta-arrestins known to regulate many nonvisual GPCRs. The dynamic and promiscuous coupling of Arr2 to nonvisual GPCRs has posed technical challenges to tackle the basis of arrestin binding to GPCRs. Here we report the structure of Arr2 in complex with neurotensin receptor 1 (NTSR1), which reveals an overall assembly that is strikingly different from the visual arrestin-rhodopsin complex by a 90 degrees rotation of Arr2 relative to the receptor. In this new configuration, intracellular loop 3 (ICL3) and transmembrane helix 6 (TM6) of the receptor are oriented toward the N-terminal domain of the arrestin, making it possible for GPCRs that lack the C-terminal tail to couple Arr2 through their ICL3. Molecular dynamics simulation and crosslinking data further support the assembly of the Arr2.NTSR1 complex. Sequence analysis and homology modeling suggest that the Arr2. NTSR1 complex structure may provide an alternative template for modeling arrestin-GPCR interactions.
资助项目	Ministry of Science and Technology (China)[2012ZX09301001] ; Ministry of Science and Technology (China)[2012CB910403] ; Ministry of Science and Technology (China)[2013CB910600] ; Ministry of Science and Technology (China)[XDB08020303] ; Ministry of Science and Technology (China)[2013ZX09507001] ; Van Andel Research Institute ; National Institutes of Health grants[GM127710] ; 100 Talents Program of the Chinese Academy of Sciences ; Chinese Academy of Sciences grant[XDA12010317] ; Natural Science Foundation of Shanghai[18ZR1447700] ; Shanghai Sailing Program[19YF1456800] ; China Postdoctoral Science Foundation[2019M651622] ; National Basic Research Program of China[2017YFA0503503] ; NSFC[31670754] ; CAS[DSS-WXJZ-2018-0002] ; CAS[CAS-SSRC-YH-2015-01] ; CAS Major Science and Technology Infrastructure Open Research Projects
WOS关键词	NEUROTENSIN ; VISUALIZATION ; RECRUITMENT ; AGONIST ; ML314
WOS研究方向	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000500749600004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281581]
专题	中国科学院上海药物研究所
通讯作者	Cong, Yao; Zhou, X. Edward; Yu, Xuekui; Xu, H. Eric
作者单位	1.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Pathol, Hangzhou 310058, Zhejiang, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Cryo Electron Microscopy Res Ctr, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol,CAS Ctr Excelle, Natl Ctr Prot Sci Shanghai,State Key Lab Mol Biol, Shanghai 200031, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Van Andel Res Inst, Program Struct Biol, Ctr Canc & Cell Biol, Grand Rapids, MI 49503 USA 7.Adamas Univ, Sch Life Sci & Biotechnol, Dept Biotechnol, Kolkata, India 8.Harbin Inst Technol, HIT Ctr Life Sci, Lab Receptor Struct & Signaling, Harbin 150001, Heilongjiang, Peoples R China 9.Zhejiang Univ, Sch Med, Dept Biophys, Hangzhou 310058, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Yin, Wanchao,Li, Zhihai,Jin, Mingliang,et al. A complex structure of arrestin-2 bound to a G protein-coupled receptor[J]. CELL RESEARCH,2019,29(12):971-983.
APA	Yin, Wanchao.,Li, Zhihai.,Jin, Mingliang.,Yin, Yu-Ling.,de Waal, Parker W..,...&Xu, H. Eric.(2019).A complex structure of arrestin-2 bound to a G protein-coupled receptor.CELL RESEARCH,29(12),971-983.
MLA	Yin, Wanchao,et al."A complex structure of arrestin-2 bound to a G protein-coupled receptor".CELL RESEARCH 29.12(2019):971-983.