Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module
Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module
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DOI：
10.1016/j.jmb.2008.04.039
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发表时间：
2008-06-27
影响因子：
5.6
通讯作者：
Ikura, Mitsuhiko
中科院分区：
文献类型：
--
作者：
Li, Guang-Yao;Zhang, Yonglong;Ikura, Mitsuhiko
大肠杆菌染色体relBE操纵子编码一个毒素-抗毒素系统，该系统由其蛋白产物RelB和RelE自动调节。RelB作为转录抑制因子，RelE作为辅助因子增强RelB的抑制活性。在这里，我们展示了RelB二聚体的核磁共振衍生结构，并表明RelB二聚体通过带状-螺旋-螺旋基序识别回文算子区域的六重体重复序列。我们的生化数据显示，两个弱关联的RelB节食者以中等亲和力(Kg（d)，类似于10(-5)M）结合在操作员（O-R）的3'位点邻近的重复序列上。然而，在RelE存在的情况下，RelB四聚体在操作区域内结合两个不同的结合位点，每个位点都具有增强的亲和力(K-d，类似于低亲和力位点O-L的10（-6)M和高亲和力位点O-R的10(-8)M）。我们提出，对操作元件的亲和力增强是由一对RelB二聚体的DNA合作结合介导的，RelB二聚体之间的相互作用被同源毒素RelE的存在强烈增强。(C) 2008 Elsevier Ltd版权所有。
The Escherichia coli chromosomal relBE operon encodes a toxin-antitoxin system, which is autoregulated by its protein products, RelB and RelE. RelB acts as a transcriptional repressor and RelE functions as a cofactor to enhance the repressor activity of RelB. Here, we present the NMR-derived structure of a RelB dimer and show that a RelB dimer recognizes a hexad repeat in the palindromic operator region through a ribbon-helix-helix motif. Our biochemical data show that two weakly associated RelB dieters bind to the adjacent repeats in the 3'-site of the operator (O-R) at a moderate affinity (Kg(d), similar to 10(-5) M). However, in the presence of RelE, a RelB tetramer binds two distinct binding sites within the operator region, each with an enhanced affinity (K-d, similar to 10(-6) M for the low-affinity site, O-L, and 10(-8) M for the high-affinity site, O-R). We propose that the enhanced affinity for the operator element is mediated by a cooperative DNA binding by a pair of RelB dimers and that the interaction between RelB dimers is strongly augmented by the presence of the cognate toxin RelE. (C) 2008 Elsevier Ltd. All rights reserved.