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2
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本文引用的文献

1
Double-stranded RNA-independent dimerization of interferon-induced protein kinase PKR and inhibition of dimerization by the cellular P58IPK inhibitor.干扰素诱导蛋白激酶PKR的双链RNA非依赖性二聚化以及细胞P58IPK抑制剂对二聚化的抑制作用。
Mol Cell Biol. 1998 May;18(5):2431-43. doi: 10.1128/MCB.18.5.2431.
2
PKR--a protein kinase regulated by double-stranded RNA.PKR——一种受双链RNA调控的蛋白激酶。
Int J Biochem Cell Biol. 1997 Jul;29(7):945-9. doi: 10.1016/s1357-2725(96)00169-0.
3
Ribosome targeting of PKR is mediated by two double-stranded RNA-binding domains and facilitates in vivo phosphorylation of eukaryotic initiation factor-2.蛋白激酶R（PKR）对核糖体的靶向作用由两个双链RNA结合结构域介导，并促进真核起始因子-2的体内磷酸化。
J Biol Chem. 1997 May 30;272(22):14434-41. doi: 10.1074/jbc.272.22.14434.
4
Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways.信号转导和转录激活因子1（STAT1）与干扰素诱导蛋白激酶PKR之间的物理关联及其对干扰素和双链RNA信号通路的影响。
EMBO J. 1997 Mar 17;16(6):1291-304. doi: 10.1093/emboj/16.6.1291.
5
A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis.一条介导应激诱导凋亡的双链RNA激活蛋白激酶依赖性途径。
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3279-83. doi: 10.1073/pnas.94.7.3279.
6
Characterization of the solution complex between the interferon-induced, double-stranded RNA-activated protein kinase and HIV-I trans-activating region RNA.干扰素诱导的双链RNA激活蛋白激酶与HIV-1反式激活区RNA之间溶液复合物的特性分析
J Biol Chem. 1997 Apr 4;272(14):9510-6. doi: 10.1074/jbc.272.14.9510.
7
The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR.人类免疫缺陷病毒1型的反式激活蛋白（Tat蛋白）是干扰素诱导的病毒激活蛋白激酶PKR的底物和抑制剂。
J Biol Chem. 1997 Mar 28;272(13):8388-95. doi: 10.1074/jbc.272.13.8388.
8
Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-kappaB.蛋白激酶R基因靶向缺失的小鼠胚胎成纤维细胞中细胞因子信号传导缺陷：干扰素调节因子-1和核因子κB的作用
EMBO J. 1997 Jan 15;16(2):406-16. doi: 10.1093/emboj/16.2.406.
9
A model for the double-stranded RNA (dsRNA)-dependent dimerization and activation of the dsRNA-activated protein kinase PKR.一种依赖双链RNA（dsRNA）的双链RNA激活蛋白激酶PKR二聚化和激活的模型。
J Biol Chem. 1997 Jan 10;272(2):1291-6. doi: 10.1074/jbc.272.2.1291.
10
Specific mutations near the amino terminus of double-stranded RNA-dependent protein kinase (PKR) differentially affect its double-stranded RNA binding and dimerization properties.双链RNA依赖性蛋白激酶（PKR）氨基末端附近的特定突变对其双链RNA结合和二聚化特性有不同影响。
J Biol Chem. 1996 Oct 11;271(41):25657-63. doi: 10.1074/jbc.271.41.25657.

蛋白激酶PKR的双链RNA结合结构域结构揭示了其双链RNA介导激活的分子基础。

Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation.

作者信息

Nanduri S, Carpick B W, Yang Y, Williams B R, Qin J

机构信息

Structural Biology Program, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

出版信息

EMBO J. 1998 Sep 15;17(18):5458-65. doi: 10.1093/emboj/17.18.5458.

DOI:10.1093/emboj/17.18.5458
PMID:9736623
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1170871/
Abstract

Protein kinase PKR is an interferon-induced enzyme that plays a key role in the control of viral infections and cellular homeostasis. Compared with other known kinases, PKR is activated by a distinct mechanism that involves double-stranded RNA (dsRNA) binding in its N-terminal region in an RNA sequence-independent fashion. We report here the solution structure of the 20 kDa dsRNA-binding domain (dsRBD) of human PKR, which provides the first three-dimensional insight into the mechanism of its dsRNA-mediated activation. The structure of dsRBD exhibits a dumb-bell shape comprising two tandem linked dsRNA-binding motifs (dsRBMs) both with an alpha-beta-beta-beta-alpha fold. The structure, combined with previous mutational and biochemical data, reveals a highly conserved RNA-binding site on each dsRBM and suggests a novel mode of protein-RNA recognition. The central linker is highly flexible, which may enable the two dsRBMs to wrap around the RNA duplex for cooperative and high-affinity binding, leading to the overall change of PKR conformation and its activation.

摘要

蛋白激酶PKR是一种干扰素诱导酶，在控制病毒感染和细胞内稳态中起关键作用。与其他已知激酶相比，PKR通过一种独特的机制被激活，该机制涉及在其N端区域以RNA序列非依赖方式结合双链RNA（dsRNA）。我们在此报告人PKR的20 kDa双链RNA结合结构域（dsRBD）的溶液结构，这首次从三维角度深入了解其dsRNA介导的激活机制。dsRBD的结构呈哑铃状，由两个串联连接的双链RNA结合基序（dsRBMs）组成，二者均具有α-β-β-β-α折叠。该结构与先前的突变和生化数据相结合，揭示了每个dsRBM上一个高度保守的RNA结合位点，并提示了一种新的蛋白质-RNA识别模式。中央连接子具有高度灵活性，这可能使两个dsRBM能够围绕RNA双链体进行协同和高亲和力结合，导致PKR构象的整体变化及其激活。