Functional role of the three conserved cysteines in the N domain of visual arrestin-1

doi:10.1074/jbc.M117.790386

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物靶标结构与功能中心

	Functional role of the three conserved cysteines in the N domain of visual arrestin-1
	Vishnivetskiy, Sergey A.1; Lee, Regina J.1,3; Zhou, X. Edward 2,5; Franz, Andreas 1,4; Xu, Qiuyi 1; Xu, H. Eric2,5 ; Gurevich, Vsevolod V.1
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2017-07-28
卷号	292 期号:30 页码:12496-12502
关键词	arrestin conformational change photoreceptor phototransduction rhodopsin activation cysteines
ISSN号	0021-9258
DOI	10.1074/jbc.M117.790386
文献子类	Article
英文摘要	Arrestins specifically bind active and phosphorylated forms of their cognate G protein-coupled receptors, blocking G protein coupling and often redirecting the signaling to alternative pathways. High-affinity receptor binding is accompanied by two major structural changes in arrestin: release of the C-tail and rotation of the two domains relative to each other. The first requires detachment of the arrestin C-tail from the body of the molecule, whereas the second requires disruption of the network of charge-charge interactions at the interdomain interface, termed the polar core. These events can be facilitated by mutations destabilizing the polar core or the anchoring of the C-tail that yield preactivated arrestins that bind phosphorylated and unphosphorylated receptors with high affinity. Here we explored the functional role in arrestin activation of the three native cysteines in the N domain, which are conserved in all arrestin subtypes. Using visual arrestin-1 and rhodopsin as a model, we found that substitution of these cysteines with serine, alanine, or valine virtually eliminates the effects of the activating polar core mutations on the binding to unphosphorylated rhodopsin while only slightly reducing the effects of the C-tail mutations. Thus, these three conserved cysteines play a role in the domain rotation but not in the C-tail release.
资助项目	National Institutes of Health[EY011500] ; National Institutes of Health[GM077561] ; National Institutes of Health[GM109955] ; National Institutes of Health[R35 GM122491] ; National Institutes of Health[DK071662]
WOS关键词	PROTEIN-COUPLED RECEPTOR ; CRYSTAL-STRUCTURE ; PHOSPHORYLATION-RECOGNITION ; CONFORMATIONAL-CHANGES ; BETA-ARRESTIN ; RHODOPSIN ; BINDING ; ACTIVATION ; SELECTIVITY ; MECHANISM
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000406636900014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272552]
专题	药物靶标结构与功能中心
通讯作者	Gurevich, Vsevolod V.
作者单位	1.Vanderbilt Univ, Nashville, TN 37232 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, VARI SIMM Ctr,Ctr Struct & Funct Drug Targets, Shanghai 201203, Peoples R China; 3.NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA; 4.Free Univ Berlin, Takustr 6, D-14195 Berlin, Germany 5.Van Andel Res Inst, Ctr Struct Biol & Drug Discovery, Lab Struct Sci, Grand Rapids, MI 49503 USA;
推荐引用方式 GB/T 7714	Vishnivetskiy, Sergey A.,Lee, Regina J.,Zhou, X. Edward,et al. Functional role of the three conserved cysteines in the N domain of visual arrestin-1[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017,292(30):12496-12502.
APA	Vishnivetskiy, Sergey A..,Lee, Regina J..,Zhou, X. Edward.,Franz, Andreas.,Xu, Qiuyi.,...&Gurevich, Vsevolod V..(2017).Functional role of the three conserved cysteines in the N domain of visual arrestin-1.JOURNAL OF BIOLOGICAL CHEMISTRY,292(30),12496-12502.
MLA	Vishnivetskiy, Sergey A.,et al."Functional role of the three conserved cysteines in the N domain of visual arrestin-1".JOURNAL OF BIOLOGICAL CHEMISTRY 292.30(2017):12496-12502.