School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
Cell Microbiol. 2014 May;16(5):673-86. doi: 10.1111/cmi.12293. Epub 2014 Apr 4.
Development of the erythrocytic malaria parasite requires targeting of parasite proteins into multiple compartments located within and beyond the parasite confine. Beyond the PEXEL/VTS pathway and its characterized players, increasing amount of evidence has highlighted the existence of proteins exported using alternative export-signal(s)/pathway(s); hence, the exportomes currently predicted are incomplete. The nature of these exported proteins which could have a prominent role in most of the Plasmodium species remains elusive. Using P. yoelii variant proteins, we identified a signal associated to lipophilic region that mediates export of P. yoelii proteins. This non-PEXEL signal termed PLASMED is defined by semi-conserved residues and possibly a secondary structure. In vivo characterization of exported-proteins indicated that PLASMED is a bona fide export-signal that allowed us to identify an unseen P. yoelii exportome. The repertoire of the newly predicted exported proteins opens up perspectives for unravelling the remodelling of the host-cell by the parasite, against which new therapies could be elaborated.
红细胞疟原虫的发育需要将寄生虫蛋白靶向到位于寄生虫内外的多个隔室中。除了 PEXEL/VTS 途径及其特征性的参与者外，越来越多的证据强调了存在使用替代输出信号/途径输出的蛋白质；因此，目前预测的输出组并不完整。这些输出蛋白的性质对于大多数疟原虫物种可能具有重要作用，但仍不清楚。使用 P. yoelii 变异蛋白，我们鉴定出与亲脂区域相关的信号，该信号介导 P. yoelii 蛋白的输出。这种非 PEXEL 信号称为 PLASMED，由半保守残基和可能的二级结构定义。对输出蛋白的体内特征分析表明，PLASMED 是一个真正的输出信号，使我们能够识别出一个看不见的 P. yoelii 输出组。新预测的输出蛋白的 repertoire 为揭示寄生虫对宿主细胞的重塑打开了前景，针对这些重塑可以设计新的治疗方法。
