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

TusA 是一种多功能蛋白质，可将大肠杆菌中的硫动员与铁稳态和转化效率联系起来

• 批准号: 262101759
• 负责人: Professorin Dr. Silke Leimkühler
• 金额: --
• 依托单位: Arbeitsgruppe für Molekulare Enzymologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/262101759?language=en
• 关键词: TusA; versatile; protein; links; sulfur

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.

硫是所有生物组织的重要因素。在大肠杆菌中，硫的硫是由L-半胱氨酸的ISC以蛋白质结合的过硫化物的形式动员，该硫硫酸盐被用作铁硫簇的生物合成的普遍硫含量，硫胺素，生物素，脂肪酸，脂肪酸，麦芽菌coofactor（Molyybenum Cofactor（Molyys Coofactor）（Molyanis）和多个杂物（Mococo）（Mococo）（MOCOCO）（MOCOCOCO）。 To accomplish these cellular roles, IscS interacts with numerous proteins. ISCS的相互作用伙伴之一是TUSA蛋白，到目前为止，已经描述了双重细胞的作用，因为TUSA作为钼辅助生物合成中的硫转移以及MNM5S2U34在TRNA的位置34的MNM5S2U34修饰的核心plane的形成。然而，先前的研究表明，TUSA的缺失会对大肠杆菌中更具细胞的途径产生多效性作用，不仅包括tRNA硫醇化和Moco生物合成，而且还对通过细核体生长型除了通过编程的核糖体杂物型对病毒感染抑制的易感性增强。此外，TUSA缺失菌株会积聚铁铁，并减少了铁硫簇含量。总体而言，这强调TUSA具有多效性细胞作用。最初的结果表明，通过协调对以ISC为中心的蛋白质相互作用网络的铁和硫的进入，TUSA对ISC的活性的调节作用。在下一个融资期内，我们希望研究TUSA对Fe-S Cluster组装组装和TRNA Thiolation的作用。我们将研究TUSA对ISCS/ISCU/CYAY复合物活性的作用。此外，将研究TUSA在细胞Fe2+积累和ROS产生中的作用。最初的研究指出，TUSA在细胞分裂中的作用是通过在涉及这些过程的蛋白质的翻译效率上发挥作用。总体而言，我们计划研究TUSA缺失菌株的多种表型，并将揭示出这种多功能蛋白在大肠杆菌中的作用的谜团。