Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Parasite Biology Group, ICGEB, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
J Proteomics. 2021 Aug 15;245:104279. doi: 10.1016/j.jprot.2021.104279. Epub 2021 Jun 2.
There are important challenges when investigating individual post-translational modifications (PTMs) or protein interaction network and delineating if PTMs or their changes and cross-talks are involved during infection, disease initiation or as a result of disease progression. Proteomics and in silico approaches now offer the possibility to complement each other to further understand the regulatory involvement of these modifications in parasites and infection biology. Accordingly, the current review highlights key expressed or altered proteins and PTMs are invisible switches that turn on and off the function of most of the proteins. PTMs include phosphorylation, glycosylation, ubiquitylation, palmitoylation, myristoylation, prenylation, acetylation, methylation, and epigenetic PTMs in P. falciparum which have been recently identified. But also other low-abundant or overlooked PTMs that might be important for the parasite's survival, infectivity, antigenicity, immunomodulation and pathogenesis. We here emphasize the PTMs as regulatory pathways playing major roles in the biology, pathogenicity, metabolic pathways, survival, host-parasite interactions and the life cycle of P. falciparum. Further validations and functional characterizations of such proteins might confirm the discovery of therapeutic targets and might most likely provide valuable data for the treatment of P. falciparum, the main cause of severe malaria in human.
当研究单个翻译后修饰（PTM）或蛋白质相互作用网络，并确定 PTM 或其变化和串扰是否参与感染、疾病起始或疾病进展时，会存在一些重要的挑战。蛋白质组学和计算方法现在提供了互补的可能性，以进一步了解这些修饰在寄生虫和感染生物学中的调节作用。因此，本综述重点介绍了关键表达或改变的蛋白质和 PTM，它们是开启和关闭大多数蛋白质功能的无形开关。PTM 包括磷酸化、糖基化、泛素化、棕榈酰化、豆蔻酰化、 prenylation、乙酰化、甲基化和疟原虫中最近发现的表观遗传 PTM。但也有其他低丰度或被忽视的 PTM，它们可能对寄生虫的生存、感染力、抗原性、免疫调节和发病机制很重要。在这里，我们强调 PTM 作为调节途径，在生物学、致病性、代谢途径、生存、宿主-寄生虫相互作用和疟原虫生命周期中发挥主要作用。对这些蛋白质的进一步验证和功能表征可能会确认治疗靶点的发现，并很可能为治疗恶性疟原虫提供有价值的数据，恶性疟原虫是人类严重疟疾的主要原因。
