Caux-Thang Christelle, Parent Aubérie, Sethu Ramakrishnan, Maïga Arhamatoulaye, Blondin Geneviève, Latour Jean-Marc, Duarte Victor
§CNRS UMR 5249, LCBM, F-38054 Grenoble, France.
†Université Grenoble Alpes, LCBM, F-38054 Grenoble, France.
ACS Chem Biol. 2015 Mar 20;10(3):682-6. doi: 10.1021/cb500783g. Epub 2014 Dec 11.
Fur family proteins, ubiquitous in prokaryotes, play a pivotal role in microbial survival and virulence in most pathogens. Metalloregulators, such as Fur and PerR, regulate the transcription of genes connected to iron homeostasis and response to oxidative stress, respectively. In Bacillus subtilis, Fur and PerR bind with high affinity to DNA sequences differing at only two nucleotides. In addition to these differences in the PerR and Fur boxes, we identify in this study a residue located on the DNA binding motif of the Fur protein that is critical to discrimination between the two close DNA sequences. Interestingly, when this residue is introduced into PerR, it lowers the affinity of PerR for its own DNA target but confers to the protein the ability to interact strongly with the Fur DNA binding sequence. The present data show how two closely related proteins have distinct biological properties just by changing a single residue.
铁摄取调节蛋白家族（Fur）在原核生物中普遍存在，在大多数病原体的微生物存活和毒力方面发挥着关键作用。金属调节蛋白，如Fur和PerR，分别调节与铁稳态和氧化应激反应相关基因的转录。在枯草芽孢杆菌中，Fur和PerR与仅两个核苷酸不同的DNA序列具有高亲和力结合。除了PerR盒和Fur盒中的这些差异外，我们在本研究中鉴定出位于Fur蛋白DNA结合基序上的一个残基，该残基对于区分两个相近的DNA序列至关重要。有趣的是，当将该残基引入PerR时，它会降低PerR对其自身DNA靶标的亲和力，但赋予该蛋白与Fur DNA结合序列强烈相互作用的能力。目前的数据表明，两个密切相关的蛋白质如何仅通过改变一个残基就具有不同的生物学特性。
