TusA is a versatile protein that links sulfur mobilization to iron homeostasis and translational efficiency in Escherichia coli

硫是所有生物的基本元素。在大肠杆菌中，硫被IscS从l -半胱氨酸中以蛋白质结合过硫化物的形式动员起来，该过硫化物被用作铁硫簇、硫胺素、生物素、硫辛酸、钼辅助因子（Moco）和某些trna中存在的几种硫代核苷的生物合成的通用硫供体。为了完成这些细胞功能，IscS与许多蛋白质相互作用。IscS的一个相互作用伙伴是TusA蛋白，迄今为止已经描述了其在细胞中的双重作用，因为TusA作为硫转移酶参与钼辅助因子的生物合成和tRNA中34位mnm5s2U34修饰核苷的形成。然而，先前的研究表明，在大肠杆菌中，tusA的缺失会对更多的细胞通路产生多效性影响，不仅包括tRNA硫代化和Moco生物合成，而且除了丝状生长表型外，还会增加程序性核糖体移框对病毒感染抑制的易感性。此外，tusA缺失菌株积累了亚铁，并降低了铁硫簇含量。总之，这强调了TusA具有多效性的细胞作用。初步结果表明，TusA通过协调铁和硫进入以IscS为中心的蛋白质相互作用网络，对IscS的活性起调节作用。在下一个资助期内，我们希望进一步详细研究TusA在Fe-S簇组装和tRNA硫代化中的作用。我们将研究TusA对IscS/IscU/CyaY复合物活性的作用。此外，TusA在细胞Fe2+积累和ROS产生中的作用将被研究。最初的研究指出TusA在细胞分裂中的作用是通过对参与这些过程的蛋白质的翻译效率起作用。总的来说，我们计划研究一种tusA缺失菌株的多种表型，并将揭示这种多功能蛋白在大肠杆菌中作用的剩余奥秘。

Sulfur is an essential element for all living organisms. In Escherichia coli, the sulfur is mobilized by IscS from L-cysteine in form of a protein-bound persulfide that is utilized as the universal sulfur-donor for the biosynthesis of iron-sulfur clusters, thiamine, biotin, lipoic acid, the molybdenum cofactor (Moco), and several thiolated nucleosides present in certain tRNAs. To accomplish these cellular roles, IscS interacts with numerous proteins. One of the interaction partners of IscS is the TusA protein, for which a dual cellular role has been described so far, since TusA is involved as sulfur transferase in molybdenum cofactor biosynthesis and in the formation of mnm5s2U34 modified nucleosides at position 34 in tRNA. However, previous studies showed that a deletion of tusA causes a pleiotropic effect on even more cellular pathways in E. coli, not only including tRNA thiolation and Moco biosynthesis, but also on the enhanced susceptibility of viral infection inhibition by programmed ribosomal frameshifting in addition to a filamentous growth phenotype. Additionally, a tusA deletion strain accumulates ferrous iron and has a reduced iron-sulfur cluster content. Overall, this emphasizes that TusA has a pleiotropic cellular role. The initial results point to a regulatory role of TusA on the activity of IscS by coordinating the iron and sulfur entry to the protein interaction network centered around IscS.In the next funding period we want to study the role of TusA for Fe-S cluster assembly and tRNA thiolations in further detail. We will investigate the role of TusA on the activity of the IscS/IscU/CyaY complex. Further, the role of TusA in cellular Fe2+ accumulation and ROS production will be investigated. Initial studies pointed to a role of TusA in cell division by having a role on the translational efficiency of proteins involved in these processes. Overall, we plan to investigate the multiple phenotypes of a tusA deletion strain and will shed light on remaining mysteries of the role of this versatile protein in E. coli.