疟原虫中的翻译后脂质修饰。

Post-translational lipid modifications in Plasmodium parasites.

机构信息

School of Medicine, Deakin University, Geelong, Victoria, Australia; The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Victoria, Australia.

出版信息

Curr Opin Microbiol. 2022 Oct;69:102196. doi: 10.1016/j.mib.2022.102196. Epub 2022 Aug 26.

DOI:10.1016/j.mib.2022.102196

PMID:36037636

Abstract

Most eukaryotic proteins undergo post-translational modifications (PTMs) that significantly alter protein properties, regulate diverse cellular processes and increase proteome complexity. Among these PTMs, lipidation plays a unique and key role in subcellular trafficking, signalling and membrane association of proteins through altering substrate function, and hydrophobicity via the addition and removal of lipid groups. Three prevalent classes of lipid modifications in Plasmodium parasites include prenylation, myristoylation, and palmitoylation that are important for regulating parasite-specific molecular processes. The enzymes that catalyse these lipid attachments have also been explored as potential drug targets for antimalarial development. In this review, we discuss these lipidation processes in Plasmodium spp. and the methodologies that have been used to identify these modifications in the deadliest species of malaria parasite, Plasmodium falciparum. We also discuss the development status of inhibitors that block these pathways.

摘要

大多数真核蛋白都经历过翻译后修饰（PTMs），这些修饰极大地改变了蛋白质的性质，调节了多种细胞过程，并增加了蛋白质组的复杂性。在这些 PTMs 中，脂质化通过添加和去除脂质基团来改变底物的功能和疏水性，在蛋白质的亚细胞运输、信号转导和膜结合中起着独特而关键的作用。疟原虫寄生虫中三种常见的脂质修饰包括 prenylation、myristoylation 和 palmitoylation，它们对于调节寄生虫特有的分子过程很重要。催化这些脂质附着的酶也被探索为抗疟药物开发的潜在药物靶点。在这篇综述中，我们讨论了疟原虫属中的这些脂质化过程，以及用于鉴定最致命的疟原虫寄生虫疟原虫中这些修饰的方法。我们还讨论了阻断这些途径的抑制剂的开发状况。