在疟疾寄生虫中,PTEX是蛋白质出口的重要纽带
Brendan Elsworth1, Kathryn Matthews2, Catherine Q Nie3
11] Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, 3004, Australia [2] Monash University, Clayton, Victoria, 3800, Australia [3].
Nature
|July 22, 2014
概括
出口蛋白质的Plasmodium转位子 (PTEX) 机器对于出口所有疟疾寄生虫蛋白质至关重要. 破坏PTEX严重损害了寄生虫的生长和毒性因子的出口,将其确定为关键的药物标.
科学领域:
- 疟疾学 疟疾学
- 分子寄生虫学 分子寄生虫学
- 贩卖蛋白质 贩卖蛋白质 是一个问题.
背景情况:
- 疟疾寄生虫出口数百种蛋白质,这些蛋白质对于毒性和生长至关重要.
- 了解蛋白质出口机制对于开发新的抗疟疾药物至关重要.
- 出口蛋白质的Plasmodium转位子 (PTEX) 复合体是这种出口中介的候选者.
研究的目的:
- 研究PTEX复合体在疟疾寄生虫中的蛋白质转位中的作用和作用范围.
- 确定PTEX是否对于各种类型的寄生虫蛋白的出口至关重要.
- 评估PTEX功能障碍对寄生虫生长和毒性的影响.
主要方法:
- 产生具有基本 (HSP101,PTEX150) 和非基本 (TRX2) PTEX组件缺陷的Plasmodium falciparum寄生虫系.
- 在寄生虫的双膜屏障之外进行蛋白质贩运的分析.
- 在体外和体外对寄生虫生长和发育的评估.
主要成果:
- 基本PTEX组件的缺陷显著减少了所有类型的出口蛋白质的贩运,包括PEXEL-motif和PEXEL-negative蛋白质.
- 表面蛋白质的输出,如PfEMP1,在PTEX敲击寄生虫中显著减少.
- PTEX功能对于血液阶段的生长至关重要,即使是适度的淘汰也会严重影响红细胞周期.
结论:
- 在疟疾寄生虫中,PTEX是蛋白质出口的中心机制.
- 对于寄生虫的生长和毒性因子的输出,PTEX是不可或缺的.
- 在疟疾治疗中,PTEX 是一个有前途的药物标.
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