Department of Oncology, University of Turin, Via Santena 5 bis, 10126 Turin, Italy.
Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina, 13, 10123 Turin, Italy.
Int J Mol Sci. 2024 Jun 2;25(11):6145. doi: 10.3390/ijms25116145.
Post-translational modifications (PTMs) are essential for regulating protein functions, influencing various fundamental processes in eukaryotes. These include, but are not limited to, cell signaling, protein trafficking, the epigenetic control of gene expression, and control of the cell cycle, as well as cell proliferation, differentiation, and interactions between cells. In this review, we discuss protein PTMs that play a key role in the malaria parasite biology and its pathogenesis. Phosphorylation, acetylation, methylation, lipidation and lipoxidation, glycosylation, ubiquitination and sumoylation, nitrosylation and glutathionylation, all of which occur in malarial parasites, are reviewed. We provide information regarding the biological significance of these modifications along all phases of the complex life cycle of spp. Importantly, not only the parasite, but also the host and vector protein PTMs are often crucial for parasite growth and development. In addition to metabolic regulations, protein PTMs can result in epitopes that are able to elicit both innate and adaptive immune responses of the host or vector. We discuss some existing and prospective results from antimalarial drug discovery trials that target various PTM-related processes in the parasite or host.
翻译后修饰(PTMs)对于调节蛋白质功能至关重要,影响真核生物中的各种基本过程。这些过程包括但不限于细胞信号传导、蛋白质运输、基因表达的表观遗传控制、细胞周期控制,以及细胞增殖、分化和细胞间相互作用。在本综述中,我们讨论了在疟原虫生物学及其发病机制中起关键作用的蛋白质翻译后修饰。对发生在疟原虫中的磷酸化、乙酰化、甲基化、脂化和脂氧化、糖基化、泛素化和类泛素化、亚硝基化和谷胱甘肽化进行了综述。我们提供了有关这些修饰在疟原虫复杂生命周期各阶段的生物学意义的信息。重要的是,不仅寄生虫,而且宿主和载体蛋白的翻译后修饰通常对寄生虫的生长和发育至关重要。除了代谢调节外,蛋白质翻译后修饰还可产生能够引发宿主或载体先天和适应性免疫反应的表位。我们讨论了一些针对寄生虫或宿主中各种与翻译后修饰相关过程的抗疟药物发现试验的现有和预期结果。