Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural Universitygrid.440622.6, Tai'an, China.
Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural Universitygrid.440622.6, Tai'an, China.
Microbiol Spectr. 2022 Apr 27;10(2):e0239421. doi: 10.1128/spectrum.02394-21. Epub 2022 Mar 24.
Ubiquitin-related modifier 1 (Urm1) is a ubiquitin-like molecule (UBL) with the ability to act as a posttranslational protein modifier. Here, we characterized the Toxoplasma gondii homolog of URM1 located in the tachyzoite cytoplasm. The total loss of the TgURM1 resulted in a significant reduction in parasite invasion, replication, and virulence in mice, revealing that TgURM1 plays a pivotal role in T. gondii survival. For TgURM1, urmylation was significantly induced by oxidative stress, and mutations of the C-terminal glycine-glycine motif of TgURM1 blocked the urmylation process. Furthermore, the TgURM1 knockout strain was intolerant to oxidative stress, suggesting that TgURM1 is involved in the oxidative stress process. TgAHP1, an alkyl hydroperoxide reductase, was screened via proximity-based protein labeling techniques and proteomics and was shown to interact with TgURM1 under oxidative stress conditions. In conclusion, TgURM1 is a UBL protein involved in the response of to oxidative stress. T. gondii has an intricate life cycle which involves multiple morphologically and physiologically distinct stages, and posttranslational modifications (PTMs) may be key regulators of protein expression at relevant life cycle stages. In recent years, ubiquitin-like proteins with modification functions have been discovered and studied, including Sumo, Rub1, ATG8, and ATG12. Ubiquitin-related modifier 1 (Urm1) is a ubiquitin-like molecule (UBL), which is considered to be the oldest ubiquitin-like system. In this study, we identified the Urm1 gene in and explored that the urmylation of Urm1 was significantly induced by oxidative stress. Fewer studies have been conducted on ubiquitin-like proteins of parasites, and our results provide theoretical support for the research of metabolic regulation and antioxidative stress processes in T. gondii.
泛素相关修饰物 1（Urm1）是一种具有作为翻译后蛋白修饰物的能力的泛素样分子（UBL）。在这里，我们对位于速殖子细胞质中的弓形虫 URM1 同源物进行了特征描述。TgURM1 的完全缺失导致寄生虫入侵、复制和在小鼠中的毒力显著降低，这表明 TgURM1 在弓形虫的生存中起着关键作用。对于 TgURM1，氧化应激显著诱导了 urmylation，并且 TgURM1 的 C 末端甘氨酸-甘氨酸基序的突变阻止了 urmylation 过程。此外，TgURM1 敲除株不能耐受氧化应激，表明 TgURM1 参与了氧化应激过程。TgAHP1，一种烷基氢过氧化物还原酶，通过基于邻近的蛋白质标记技术和蛋白质组学筛选，并在氧化应激条件下显示与 TgURM1 相互作用。总之，TgURM1 是一种参与弓形虫对氧化应激反应的 UBL 蛋白。弓形虫具有复杂的生命周期，涉及多个形态和生理上不同的阶段，翻译后修饰（PTMs）可能是相关生命周期阶段蛋白质表达的关键调节剂。近年来，具有修饰功能的泛素样蛋白已被发现并研究，包括 Sumo、Rub1、ATG8 和 ATG12。泛素相关修饰物 1（Urm1）是一种泛素样分子（UBL），被认为是最古老的泛素样系统。在这项研究中，我们鉴定了弓形虫中的 Urm1 基因，并探讨了 Urm1 的 urmylation 被氧化应激显著诱导。对寄生虫的泛素样蛋白的研究较少，我们的结果为弓形虫代谢调控和抗氧化应激过程的研究提供了理论支持。
