Crystal structure of the [2Fe-2S] oxidative-stress sensor SoxR bound to DNA
Crystal structure of the [2Fe-2S] oxidative-stress sensor SoxR bound to DNA
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DOI：
10.1073/pnas.0709188105
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发表时间：
2008-03
期刊：
影响因子：
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通讯作者：
Satoshi Watanabe;A. Kita;Kazuo Kobayashi;K. Miki
中科院分区：
文献类型：
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作者：
Satoshi Watanabe;A. Kita;Kazuo Kobayashi;K. Miki
[2Fe-2S]转录因子SoxR是MerR家族的成员，作为氧化应激（如超氧化物和一氧化氮）的细菌传感器发挥作用。通过[2Fe-2S]簇的可逆单电子氧化激活SoxR，然后通过soxRS调节子增强各种抗氧化蛋白的产生。在活性状态下，SoxR和其他MerR家族蛋白通过解旋启动子DNA激活独特启动子的转录，这些启动子在-35和-10操纵元件之间具有长的19或20 bp间隔区。在这里，我们展示了SoxR的晶体结构及其与氧化（活性）状态下的目标启动子的复合物。结构表明，[2Fe-2S]簇的SoxR是完全暴露的溶剂和周围的不对称环境稳定的相互作用与其他亚基。[2Fe-2S]簇的不对称电荷环境可能导致SoxR和靶启动子的氧化还原依赖性构象变化。与先前研究的具有19-bp间隔区的启动子结构相比，DNA结构更急剧地弯曲，弯曲了0.21 bp，其中两个中心碱基对保持Watson-Crick碱基对。比较MerR家族的靶启动子序列表明，本DNA结构代表MerR家族中具有20-bp间隔子的靶启动子的活化构象。
The [2Fe-2S] transcription factor SoxR, a member of the MerR family, functions as a bacterial sensor of oxidative stress such as superoxide and nitric oxide. SoxR is activated by reversible one-electron oxidation of the [2Fe-2S] cluster and then enhances the production of various antioxidant proteins through the soxRS regulon. In the active state, SoxR and other MerR family proteins activate transcription from unique promoters, which have a long 19- or 20-bp spacer between the −35 and −10 operator elements, by untwisting the promoter DNA. Here, we show the crystal structures of SoxR and its complex with the target promoter in the oxidized (active) state. The structures reveal that the [2Fe-2S] cluster of SoxR is completely solvent-exposed and surrounded by an asymmetric environment stabilized by interaction with the other subunit. The asymmetrically charged environment of the [2Fe-2S] cluster probably causes redox-dependent conformational changes of SoxR and the target promoter. Compared with the promoter structures with the 19-bp spacer previously studied, the DNA structure is more sharply bent, by ≈1 bp, with the two central base pairs holding Watson–Crick base pairs. Comparison of the target promoter sequences of the MerR family indicates that the present DNA structure represents the activated conformation of the target promoter with a 20-bp spacer in the MerR family.