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

硫是所有生物体的必需元素。在大肠杆菌中，硫通过IscS从L-半胱氨酸以蛋白质结合的过硫化物的形式移动，其用作铁硫簇、硫胺素、生物素、硫辛酸、钼辅因子（Moco）和存在于某些tRNA中的几种硫醇化核苷的生物合成的通用硫供体。为了完成这些细胞作用，IscS与许多蛋白质相互作用。IscS的相互作用伴侣之一是杜莎蛋白，迄今为止已经描述了其双重细胞作用，因为杜莎作为硫转移酶参与钼辅因子生物合成和形成tRNA中34位的mnm 5s 2U 34修饰核苷。然而，先前的研究表明，杜莎的缺失导致了对大肠杆菌中更多细胞通路的多效性效应。大肠杆菌，不仅包括tRNA巯基化和Moco生物合成，而且还对病毒感染抑制的易感性增强，除了丝状生长表型外，还通过程序性核糖体移码。此外，一个杜莎缺失菌株积累亚铁，并具有减少的铁-硫簇含量。总的来说，这强调了杜莎具有多效性细胞作用。初步结果表明，杜莎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的活性具有调节作用。在下一个资助期，我们希望进一步详细研究杜莎对Fe-S簇组装和tRNA巯基化的作用。我们将研究杜莎对IscS/IscU/CyaY复合物活性的作用。此外，还将研究杜莎在细胞Fe 2+积累和ROS产生中的作用。最初的研究指出，杜莎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，我们计划研究杜莎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的作用的剩余奥秘。杆菌

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.