Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii.
Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii.
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Uba1：弓形虫中 Urm1 的潜在泛素样激活蛋白
DOI：
10.3390/ijms231810298
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发表时间：
2022-09-07
影响因子：
5.6
通讯作者：
Zhang, Xiao
中科院分区：
文献类型：
--
作者：
Xiao, Qianqian;Li, Jinxuan;Chen, Junpeng;Tan, Qianqian;Chen, Xiao;Li, Hongmei;Zhao, Xiaomin;Zhang, Xiao
我们在前期的研究中发现，TgUrm 1（ubiquitin-related Modifiers 1）通过与TgAhp 1结合参与了弓形虫抗氧化应激的调控。一般认为Urm 1通过涉及乌巴（泛素样激活蛋白）的机制与靶蛋白结合。在这里，我们确定了TgUrm 1专有的泛素样激活剂-TgUba 1，这是位于弓形虫的细胞质。TgUba 1含有三个结构域，包括萎缩蛋白-1结构域（Ant 1）、E1样结构域（AD）和罗丹斯同源结构域（RHD）。我们研究了TgUba 1与TgUrm 1的相互作用，发现AD结构域是两个蛋白相互作用的关键。基于CRISPR/Cas9基因编辑技术获得TgUba 1敲除和互补突变体。TgUba 1基因敲除可减弱寄生虫在小鼠体内的增殖和毒力，但不影响寄生虫的侵袭和排出过程，揭示了TgUba 1在T.弓形虫存活率同时，在没有TgUba 1的氧化应激刺激下，TgUrm 1的缀合带显著减少，表明TgUba 1增强了TgUrm 1响应氧化应激的靶向缀合能力，特别是在二酰胺（Dia）刺激下。此外，11 TgUba 1相互作用的蛋白质被确定为基于邻近的蛋白质标记技术，将它们与泛素样修饰，抗氧化应激和代谢调节过程。TgUba 1是T.可能是TgUrm 1潜在的泛素样激活蛋白。
We had shown in our previous study that TgUrm1 (ubiquitin-related Modifier 1) was involved in the regulation of anti-oxidant stress in Toxoplasma gondii by conjugating with TgAhp1. It is generally believed that Urm1 binds to target proteins through a mechanism involving Uba (ubiquitin-like activator protein). Here, we identified the TgUrm1-exclusive ubiquitin-like activator-TgUba1, which was located in the cytoplasm of Toxoplasma. TgUba1 contained three domains, including the atrophin-1 domain (ANT1), the E1-like domain (AD), and the rhodanese homology domain (RHD). We explored the interaction of TgUba1 with TgUrm1, and the AD domain was essential for the interaction of the two proteins. The TgUba1 knockout and complementary mutants were obtained based on CRISPR/Cas9 gene editing technology. The knockout of TgUba1 attenuated parasite proliferation and virulence in mice, but not invasion and egress processes, revealing the pivotal role played by TgUba1 in T. gondii survival. Meanwhile, the conjugate band of TgUrm1 was significantly reduced under oxidative stress stimulation without TgUba1, indicating that TgUba1 enhanced the targeted conjugation ability of TgUrm1 in response to oxidative stress, especially under diamide (Dia) stimulation. Furthermore, eleven TgUba1-interacting proteins were identified by proximity-based protein labeling techniques, relating them to ubiquitin-like modifications, anti-oxidative stress and metabolic regulation processes. In conclusion, TgUba1 was essential for T. gondii survival and might be a potential ubiquitin-like activator protein for TgUrm1.
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