Direct nitric oxide signal transduction via nitrosylation of iron-sulfur centers in the SoxR transcription activator
Direct nitric oxide signal transduction via nitrosylation of iron-sulfur centers in the SoxR transcription activator
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DOI：
10.1073/pnas.97.10.5146
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发表时间：
2000-05-09
影响因子：
11.1
通讯作者：
Demple, B
中科院分区：
文献类型：
--
作者：
Ding, HG;Demple, B
一氧化氮（NO）在细胞间通讯和（在更高水平）免疫介导的细胞kilting中具有不同的作用。NO与许多细胞靶点反应，细胞杀伤效应与通过铁硫中心的亚硝基化使关键酶失活相关。SoxR蛋白，一种依赖于其双核铁硫氧化态的氧化还原敏感性转录激活因子（[2Fe-2S]）中心，也在大肠杆菌中被激活，暴露于巨噬细胞产生的NO。我们在这里表明，SoxR激活NO发生通过直接修饰的[2Fe-2S]中心，形成蛋白质结合的二亚硝基铁二硫醇加合物，我们已经在完整的细菌细胞和NO处理后纯化的SoxR中观察到了这一点。通过铁-硫中心的亚硝基化的功能活化与通常由这种修饰引起的失活形成对比。纯化的亚硝基化SoxR具有与氧化SoxR相似的转录活性，并且相对稳定。相反，亚硝基化的SoxR在完整细胞中的寿命很短，这表明亚硝基化的铁-硫中心被主动处理的机制。
Nitric oxide (NO) has diverse roles in intercellular communication and (at higher levels) in immune-mediated cell kilting. NO reacts with many cellular targets, with cell-killing effects correlated to inactivation of key enzymes through nitrosylation of their iron-sulfur centers. SoxR protein, a redox-sensitive transcription activator dependent on the oxidation state of its binuclear iron-sulfur ([2Fe-2S]) centers, is also activated in Escherichia coli on exposure to macrophage-generated NO. We show here that SoxR activation by NO occurs through direct modification of the [2Fe-2S] centers to form protein-bound dinitrosyl-iron-dithiol adducts, which we have observed both in intact bacterial cells and in purified SoxR after NO treatment. Functional activation through nitrosylation of iron-sulfur centers contrasts with the inactivation typically caused by this modification. Purified, nitrosylated SoxR has transcriptional activity similar to that of oxidized SoxR and is relatively stable. In contrast, nitrosylated SoxR is short-lived in intact cells, indicative of mechanisms that actively dispose of nitrosylated iron-sulfur centers.