The Fur repressor controls transcription of iron-activated and -repressed genes in Helicobacter pylori
The Fur repressor controls transcription of iron-activated and -repressed genes in Helicobacter pylori
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DOI：
10.1046/j.1365-2958.2001.02696.x
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发表时间：
2001-12-01
影响因子：
3.6
通讯作者：
Scarlato, V
中科院分区：
文献类型：
--
作者：
Delany, I;Spohn, G;Scarlato, V
铁摄取调节蛋白（Fur）被认为是细菌启动子的铁离子依赖转录抑制因子。在这里，我们表明，在幽门螺杆菌中，皮毛可以介导铁激活基因的调节，而不是经典的皮毛调节，其中铁作为共同抑制因子。幽门螺杆菌染色体上的毛皮基因失活导致一个19 kDa蛋白的表达降低，通过n端测序鉴定该蛋白为非含血铁蛋白（Pfr）。野生型幽门螺杆菌在FeSO4浓度增加的培养基上生长，诱导P-pfr启动子的转录，相反，铁的消耗导致P-pfr的抑制，表明该启动子是铁激活的。在fur突变体中，P-pfr启动子组成型高表达，不再响应铁，表明fur蛋白介导这种类型的铁调控。足迹分析表明，Fur与P-pfr启动子区结合，Fe2+降低了结合效率。相反，Fe2+增加了Fur对经典的Fur调控启动子（铁抑制的frpB基因启动子）的亲和力。据我们所知，这是Fur蛋白和铁激活基因启动子之间直接相互作用的第一个证据。我们的研究结果支持一个模型，在这个模型中，Fur蛋白的铁状态不同地改变了它对铁抑制或铁激活基因中操作符的亲和力。
The ferric uptake regulator (Fur) protein is known to act as a Fe2+-dependent transcriptional repressor of bacterial promoters. Here, we show that, in Helicobacter pylori, Fur can mediate the regulation of iron-activated genes in contrast to classical Fur regulation, in which iron acts as a co-repressor. Inactivation of the fur gene in the chromosome of H. pylori resulted in the derepression of a 19 kDa protein that was identified by N-terminal sequencing as the non-haem-containing ferritin (Pfr). Growth of the wild-type H. pylori strain on media treated with increasing concentrations of FeSO4 resulted in induction of transcription from the P-pfr promoter and, conversely, depletion of iron resulted in repression of P-pfr, indicating that this promoter is iron activated. In the fur mutant, the P-pfr promoter is constitutively highly expressed and no longer responds to iron, indicating that the Fur protein mediates this type of iron regulation. Footprinting analysis revealed that Fur binds to the P-pfr promoter region and that Fe2+ decreases the efficiency of binding. In contrast, Fe2+ increased the affinity of Fur for a classical Fur-regulated promoter, the iron-repressed frpB gene promoter. To our knowledge, this is the first evidence of direct interaction between the Fur protein and the promoter of an iron-activated (-derepressed) gene. Our results support a model in which the iron status of the Fur protein differentially alters its affinity for operators in either iron-repressed or iron-activated genes.