Malaria Programme, The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Cell Host Microbe. 2012 Aug 16;12(2):246-58. doi: 10.1016/j.chom.2012.06.005.
Asexual stage Plasmodium falciparum replicates and undergoes a tightly regulated developmental process in human erythrocytes. One mechanism involved in the regulation of this process is posttranslational modification (PTM) of parasite proteins. Palmitoylation is a PTM in which cysteine residues undergo a reversible lipid modification, which can regulate target proteins in diverse ways. Using complementary palmitoyl protein purification approaches and quantitative mass spectrometry, we examined protein palmitoylation in asexual-stage P. falciparum parasites and identified over 400 palmitoylated proteins, including those involved in cytoadherence, drug resistance, signaling, development, and invasion. Consistent with the prevalence of palmitoylated proteins, palmitoylation is essential for P. falciparum asexual development and influences erythrocyte invasion by directly regulating the stability of components of the actin-myosin invasion motor. Furthermore, P. falciparum uses palmitoylation in diverse ways, stably modifying some proteins while dynamically palmitoylating others. Palmitoylation therefore plays a central role in regulating P. falciparum blood stage development.
无性阶段疟原虫在人体红细胞中复制并经历严格调控的发育过程。参与该过程调控的机制之一是寄生虫蛋白的翻译后修饰（PTM）。棕榈酰化是一种翻译后修饰，其中半胱氨酸残基发生可逆的脂质修饰，可通过多种方式调节靶蛋白。我们使用互补的棕榈酰蛋白纯化方法和定量质谱法，研究了无性阶段疟原虫中的蛋白棕榈酰化，并鉴定了 400 多种棕榈酰化蛋白，包括参与细胞黏附、耐药性、信号转导、发育和入侵的蛋白。与棕榈酰化蛋白的普遍性一致，棕榈酰化对于疟原虫无性发育是必需的，并且通过直接调节肌动球蛋白入侵马达的组成部分的稳定性来影响红细胞入侵。此外，疟原虫以多种方式使用棕榈酰化，稳定修饰一些蛋白，同时动态棕榈酰化其他蛋白。因此，棕榈酰化在调节疟原虫血期发育中起着核心作用。
