Brown Robert W B, Sharma Aabha I, Engman David M
a Department of Pathology and Laboratory Medicine , Cedars-Sinai Medical Center , Los Angeles , CA , USA.
b Departments of Pathology and Microbiology-Immunology , Northwestern University , Chicago , IL , USA.
Crit Rev Biochem Mol Biol. 2017 Apr;52(2):145-162. doi: 10.1080/10409238.2017.1287161. Epub 2017 Feb 20.
Eukaryotic parasites possess complex life cycles and utilize an assortment of molecular mechanisms to overcome physical barriers, suppress and/or bypass the host immune response, including invading host cells where they can replicate in a protected intracellular niche. Protein S-palmitoylation is a dynamic post-translational modification in which the fatty acid palmitate is covalently linked to cysteine residues on proteins by the enzyme palmitoyl acyltransferase (PAT) and can be removed by lysosomal palmitoyl-protein thioesterase (PPT) or cytosolic acyl-protein thioesterase (APT). In addition to anchoring proteins to intracellular membranes, functions of dynamic palmitoylation include - targeting proteins to specific intracellular compartments via trafficking pathways, regulating the cycling of proteins between membranes, modulating protein function and regulating protein stability. Recent studies in the eukaryotic parasites - Plasmodium falciparum, Toxoplasma gondii, Trypanosoma brucei, Cryptococcus neoformans and Giardia lamblia - have identified large families of PATs and palmitoylated proteins. Many palmitoylated proteins are important for diverse aspects of pathogenesis, including differentiation into infective life cycle stages, biogenesis and tethering of secretory organelles, assembling the machinery powering motility and targeting virulence factors to the plasma membrane. This review aims to summarize our current knowledge of palmitoylation in eukaryotic parasites, highlighting five exemplary mechanisms of parasite virulence dependent on palmitoylation.
真核寄生虫具有复杂的生命周期，并利用多种分子机制来克服物理屏障、抑制和/或绕过宿主免疫反应，包括侵入宿主细胞，在受保护的细胞内微环境中进行复制。蛋白质S-棕榈酰化是一种动态的翻译后修饰，其中脂肪酸棕榈酸通过棕榈酰酰基转移酶（PAT）与蛋白质上的半胱氨酸残基共价连接，并可被溶酶体棕榈酰蛋白硫酯酶（PPT）或胞质酰基蛋白硫酯酶（APT）去除。除了将蛋白质锚定到细胞内膜上，动态棕榈酰化的功能还包括——通过运输途径将蛋白质靶向特定的细胞内区室、调节蛋白质在膜之间的循环、调节蛋白质功能以及调节蛋白质稳定性。最近对真核寄生虫——恶性疟原虫、刚地弓形虫、布氏锥虫、新型隐球菌和蓝氏贾第鞭毛虫——的研究已经鉴定出了大量的PAT家族和棕榈酰化蛋白。许多棕榈酰化蛋白在发病机制的各个方面都很重要，包括分化为感染性生命周期阶段、分泌细胞器的生物发生和系留、组装驱动运动的机制以及将毒力因子靶向质膜。本综述旨在总结我们目前对真核寄生虫中棕榈酰化的认识，重点介绍依赖棕榈酰化的寄生虫毒力的五种典型机制。
