Functional role of the three conserved cysteines in the N domain of visual arrestin-1
文献类型：期刊论文
| 作者 | Vishnivetskiy, Sergey A.1; Lee, Regina J.1,3; Zhou, X. Edward2,5; Franz, Andreas1,4; Xu, Qiuyi1; Xu, H. Eric2,5 ; Gurevich, Vsevolod V.1
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 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. |
| WOS关键词 | PROTEIN-COUPLED RECEPTOR ; CRYSTAL-STRUCTURE ; PHOSPHORYLATION-RECOGNITION ; CONFORMATIONAL-CHANGES ; BETA-ARRESTIN ; RHODOPSIN ; BINDING ; ACTIVATION ; SELECTIVITY ; MECHANISM |
| 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研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000406636900014 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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