Systematic identification of the lysine lactylation in the protozoan parasite Toxoplasma gondii.
Systematic identification of the lysine lactylation in the protozoan parasite Toxoplasma gondii.
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DOI：
10.1186/s13071-022-05315-6
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发表时间：
2022-05-24
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
赖氨酸乳酸化（Lysine lactyation, Kla）是一种在真核细胞组蛋白和非组蛋白中发现的新型翻译后修饰（PTM），可直接激活基因表达和DNA复制。然而，尽管Kla在公共和动物卫生保健中具有重要意义，但对其在顶复体寄生虫中的范围和细胞分布知之甚少。刚地弓形虫是弓形虫病的病原体，是一种专性细胞内的顶复合体寄生虫，可感染动物和人类的不同有核细胞类型。我们以弓形虫为模型生物，通过液相色谱-串联质谱法提取了弓形虫速殖子的总蛋白，得到了弓形虫赖氨酸乳酸酶的第一个全局谱。我们还分别利用western blotting和间接荧光抗体试验（IFA）研究了Kla蛋白在弓形虫体内的水平和定位。在急性期弓形虫速殖子提取的总蛋白中，共鉴定出523个乳酸化蛋白上的983个Kla位点。生物信息学分析表明，乳酸化蛋白具有进化保守性，并参与多种细胞功能，如能量代谢、基因调控和蛋白质生物合成。亚细胞定位分析和IFA结果进一步显示，大部分乳酸化的弓形虫蛋白定位在细胞核中，这表明Kla对弓形虫模型中基因调控的潜在影响。值得注意的是，弓形虫体内有大量的顶复合体门特有的寄生虫特异性蛋白质被乳酸化。这项研究表明Kla在早期分裂的真核细胞中广泛存在。乳酸化蛋白，包括一批独特的寄生虫蛋白，参与了一系列非常多样化的细胞功能。这些有价值的数据将提高我们对Kla进化的理解，并可能为开发新的治疗途径提供基础。在线版本包含补充材料，可在10.1186/s13071-022-05315-6获得。
Lysine lactylation (Kla) is a novelposttranslational modification (PTM) identified in histone and nonhistone proteins of several eukaryotic cells that directly activates gene expression and DNA replication. However, very little is known about the scope and cellular distribution of Kla in apicomplexan parasites despite its significance in public and animal health care. Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular apicomplexan parasite that can infect different nucleated cell types of animals and humans. We used this parasite as a model organism and extracted the total protein of tachyzoites to produce the first global lysine lactylome profile of T. gondii through liquid chromatography–tandem mass spectrometry. We also investigated the level and localization of the Kla protein in T. gondii using western blotting and the indirect fluorescent antibody test (IFA), respectively. A total of 983 Kla sites occurring on 523 lactylated proteins were identified in the total protein extracted from Toxoplasma tachyzoites, the acute toxoplasmosis-causing stage. Bioinformatics analysis revealed that the lactylated proteins were evolutionarily conserved and involved in a wide variety of cellular functions, such as energy metabolism, gene regulation and protein biosynthesis. Subcellular localization analysis and IFA results further revealed that most of the lactylated T. gondii proteins were localized in the nucleus, indicating the potential impact of Kla on gene regulation in the T. gondii model. Notably, an extensive batch of parasite-specific proteins unique to phylum Apicomplexa is lactylated in T. gondii. This study revealed that Kla is widespread in early dividing eukaryotic cells. Lactylated proteins, including a batch of unique parasite proteins, are involved in a remarkably diverse array of cellular functions. These valuable data will improve our understanding of the evolution of Kla and potentially provide the basis for developing novel therapeutic avenues. The online version contains supplementary material available at 10.1186/s13071-022-05315-6.
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影响因子：
3.7
作者：
Abdelbaset AE;Fox BA;Karram MH;Abd Ellah MR;Bzik DJ;Igarashi M
通讯作者：
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影响因子：
14.9
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