Howard Hughes Medical Institute, Washington University School of Medicine, Department of Molecular Microbiology, St Louis, Missouri 63110, USA.
Nature. 2010 Feb 4;463(7281):632-6. doi: 10.1038/nature08726.
During their intraerythrocytic development, malaria parasites export hundreds of proteins to remodel their host cell. Nutrient acquisition, cytoadherence and antigenic variation are among the key virulence functions effected by this erythrocyte takeover. Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development.
在其红细胞内发育过程中，疟原虫向宿主细胞输出数百种蛋白以重塑其细胞。营养物质摄取、细胞黏附和抗原变异是这种红细胞接管所产生的关键毒力功能之一。注定要输出的蛋白质在内质网 (ER) 中合成，并在保守的 (PEXEL) 基序处被切割，该基序允许通过称为 PTEX 复合物的 ATP 驱动转位器进入宿主细胞。我们报告说，与哺乳动物加工酶 BACE 具有远缘同源性的内质网天冬氨酸蛋白酶 plasmepsin V 识别 PEXEL 基序并在正确的位点切割它。这种酶对寄生虫的生存能力至关重要，内质网的驻留对其功能至关重要。我们提出 plasmepsin V 是 PEXEL 蛋白酶，是抗疟药物开发的有吸引力的酶。
