Target-selective protein S-nitrosylation by sequence motif recognition.
Target-selective protein S-nitrosylation by sequence motif recognition.
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DOI：
10.1016/j.cell.2014.09.032
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发表时间：
2014-10-23
期刊：
影响因子：
64.5
通讯作者：
Fox PL
中科院分区：
文献类型：
--
作者：
Jia J;Arif A;Terenzi F;Willard B;Plow EF;Hazen SL;Fox PL
S-亚硝基化是一种普遍存在的蛋白质修饰，是一氧化氮（NO）介导的信号转导和细胞功能的主要机制。S-亚硝基化酶可以利用NO合酶（NOS）衍生的NO修饰靶蛋白中选定的半胱氨酸。尽管蛋白质组学鉴定了超过一千种S-亚硝基化蛋白，但很少有S-亚硝基化酶被鉴定出来。此外，位点选择性S-亚硝基化的潜在机制和特定序列基序的潜在作用在很大程度上仍然未知。在这里，我们描述了一个刺激诱导，异源三聚体S-亚硝基酶复合物组成的诱导型一氧化氮合酶（iNOS），S100 A8，和S100 A9。S100 A9具有转亚硝基酶活性，将NO从iNOS穿梭到靶蛋白，而S100 A8和S100 A9协调指导位点选择。通过蛋白质组学分析揭示了一个被iNOS-S100 A8/A9复合物S-亚硝基化的蛋白质家族，并验证了其为靶标。保守的I/L-X-C-X2-D/E基序是iNOS-S100 A8/A9介导的S-亚硝基化所必需和充分的。这些结果揭示了蛋白质S-亚硝基化和磷酸化之间的难以捉摸的平行，即，刺激依赖性的翻译后修饰所选择的目标的主要序列基序识别。
S-nitrosylation is a ubiquitous protein modification emerging as a principal mechanism of nitric oxide (NO)-mediated signal transduction and cell function. S-nitrosylases can use NO synthase (NOS)-derived NO to modify selected cysteines in target proteins. Despite proteomic identification of more than a thousand S-nitrosylated proteins, very few S-nitrosylases have been identified. Moreover, mechanisms underlying site-selective S-nitrosylation and the potential role of specific sequence motifs remain largely unknown. Here, we describe a stimulus-inducible, heterotrimeric S-nitrosylase complex consisting of inducible NOS (iNOS), S100A8, and S100A9. S100A9 exhibits transnitrosylase activity, shuttling NO from iNOS to the target protein, whereas S100A8 and S100A9 coordinately direct site selection. A family of proteins S-nitrosylated by the iNOS-S100A8/A9 complex were revealed by proteomic analysis, and validated as targets. A conserved I/L-X-C-X2-D/E motif was necessary and sufficient for iNOS- S100A8/A9-mediated S-nitrosylation. These results reveal an elusive parallel between protein S-nitrosylation and phosphorylation, namely, stimulus-dependent post-translational modification of selected targets by primary sequence motif recognition.
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影响因子：
4.4
作者：
Chen, Yi-Ju;Ku, Wei-Chi;Chen, Yu-Ju
通讯作者：
Chen, Yu-Ju
影响因子：
37.8
作者：
Croce K;Gao H;Wang Y;Mooroka T;Sakuma M;Shi C;Sukhova GK;Packard RR;Hogg N;Libby P;Simon DI
通讯作者：
Simon DI
DOI：
10.1161/atvbaha.109.190314
发表时间：
2009-08-01
影响因子：
8.7
作者：
Ionita, Mihaela G.;Vink, Aryan;de Kleijn, Dominique P. V.
通讯作者：
de Kleijn, Dominique P. V.
影响因子：
5.8
作者：
Buzko, O;Shokat, KM
通讯作者：
Shokat, KM
DOI：
10.1073/pnas.1008036107
发表时间：
2010-09-28
影响因子：
11.1
作者：
Doulias, Paschalis-Thomas;Greene, Jennifer L.;Ischiropoulos, Harry
通讯作者：
Ischiropoulos, Harry