Osborne Andrew R, Speicher Kaye D, Tamez Pamela A, Bhattacharjee Souvik, Speicher David W, Haldar Kasturi
Center for Rare and Neglected Diseases, University of Notre Dame, 103 Galvin Life Sciences, South Bend, IN 46556, USA.
Mol Biochem Parasitol. 2010 May;171(1):25-31. doi: 10.1016/j.molbiopara.2010.01.003. Epub 2010 Feb 1.
During the blood stage of its lifecycle, the malaria parasite resides and replicates inside a membrane vacuole within its host cell, the human erythrocyte. The parasite exports many proteins across the vacuole membrane and into the host cell cytoplasm. Most exported proteins are characterized by the presence of a host targeting (HT) motif, also referred to as a Plasmodium export element (PEXEL), which corresponds to the consensus sequence RxLxE/D/Q. During export the HT motif is cleaved by an unknown protease. Here, we generate parasite lines expressing HT motif containing proteins that are localized to different compartments within the parasite or host cell. We find that the HT motif in a protein that is retained in the parasite endoplasmic reticulum is cleaved and N-acetylated as efficiently as a protein that is exported. This shows that cleavage of the HT motif occurs early in the secretory pathway, in the parasite endoplasmic reticulum.
在其生命周期的血液阶段，疟原虫寄生于其宿主细胞——人类红细胞内的一个膜泡中并在其中进行复制。疟原虫会将许多蛋白质输出穿过液泡膜进入宿主细胞质。大多数输出蛋白的特征是存在一个宿主靶向（HT）基序，也称为疟原虫输出元件（PEXEL），它对应于共有序列RxLxE/D/Q。在输出过程中，HT基序被一种未知蛋白酶切割。在这里，我们构建了表达含有HT基序的蛋白质的寄生虫系，这些蛋白质定位于寄生虫或宿主细胞内的不同区室。我们发现，保留在寄生虫内质网中的蛋白质中的HT基序与被输出的蛋白质一样有效地被切割并进行N - 乙酰化。这表明HT基序的切割发生在分泌途径的早期，即在寄生虫内质网中。
