Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.
Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Sci Rep. 2018 May 8;8(1):7140. doi: 10.1038/s41598-018-25157-6.
Ferric uptake regulators (Fur) are a family of transcription factors coupling gene regulatory events to metal concentration. Recent evidence has expanded the mechanistic repertoires employed by Fur to activate or repress gene expression in the presence or absence of regulatory metals. However, the mechanistic basis underlying this extended repertoire has remained largely unexplored. In this study, we used an extensive set of mutations to demonstrate that Campylobacter jejuni Fur (CjFur) employs the same surface to positively and negatively control gene expression regardless of the presence or absence of metals. Moreover, the crystal structure determination of a CjFur devoid of any regulatory metals shows that subtle reorientation of the transcription factor DNA binding domain negatively impacts DNA binding, gene expression and gut colonization in chickens. Overall, these results highlight the versatility of the CjFur DNA binding domain in mediating all gene regulatory events controlled by the metalloregulator and that the full metalation of CjFur is critical to the Campylobacter jejuni life cycle in vivo.
铁摄取调控因子（Fur）是一类转录因子，可将基因调控事件与金属浓度偶联。最近的证据扩展了 Fur 用于在存在或不存在调节金属的情况下激活或抑制基因表达的机制范围。然而，这种扩展的机制基础在很大程度上仍未得到探索。在这项研究中，我们使用了一系列广泛的突变来证明空肠弯曲菌 Fur（CjFur）无论是否存在金属，都使用相同的表面来正向和负向控制基因表达。此外，缺乏任何调节金属的 CjFur 的晶体结构测定表明，转录因子 DNA 结合域的细微重排会负向影响 DNA 结合、基因表达和鸡肠道定植。总体而言，这些结果突出了 CjFur DNA 结合域在介导金属调控因子控制的所有基因调控事件中的多功能性，并且 CjFur 的完全金属化对于空肠弯曲菌在体内的生命周期至关重要。
