Center for Rare and Neglected Diseases, University of Notre Dame, 103 Galvin Life Sciences, Notre Dame, IN 46556, USA.
Trends Parasitol. 2012 Dec;28(12):555-62. doi: 10.1016/j.pt.2012.09.004. Epub 2012 Oct 16.
Blood stage malaria parasites target a 'secretome' of hundreds of proteins including virulence determinants containing a host (cell) targeting (HT) signal, to human erythrocytes. Recent studies reveal that the export mechanism is due to the HT signal binding to the lipid phosphatidylinositol-3-phosphate [PI(3)P] in the parasite endoplasmic reticulum (ER). An aspartic protease plasmepsin V which cleaves a specialized form of the HT signal was previously thought to be the export mechanism, but is now recognized as a dedicated peptidase that cleaves the signal anchor subsequent to PI(3)P binding. We discuss a model of PI(3)P-dependent targeting and PI(3)P biology of a major human pathogen.
血阶段疟原虫以数百种蛋白质的“分泌组”为目标,包括含有宿主(细胞)靶向(HT)信号的毒力决定簇,以靶向人类红细胞。最近的研究表明,出口机制是由于 HT 信号与寄生虫内质网(ER)中的脂质磷脂酰肌醇-3-磷酸 [PI(3)P] 结合。先前认为天冬氨酸蛋白酶 plasmepsin V 是一种切割 HT 信号的特殊形式的出口机制,但现在被认为是一种专门的肽酶,在与 PI(3)P 结合后切割信号锚。我们讨论了一种依赖 PI(3)P 的靶向和主要人类病原体的 PI(3)P 生物学模型。