Role of the Plasmodium Export Element in Trafficking Parasite Proteins to the Infected Erythrocyte
Role of the Plasmodium Export Element in Trafficking Parasite Proteins to the Infected Erythrocyte
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DOI：
10.1111/j.1600-0854.2008.00864.x
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发表时间：
2009-03-01
期刊：
影响因子：
4.5
通讯作者：
Cowman, Alan F.
中科院分区：
文献类型：
--
作者：
Boddey, Justin A.;Moritz, Robert L.;Cowman, Alan F.
恶性疟原虫在人红细胞内的细胞内存活依赖于重塑宿主细胞的寄生虫蛋白的输出。大多数输出的蛋白质需要一个保守的基序（RxLxE/Q/D），称为疟原虫输出元件（PEXEL）或空泡靶向序列（VTS），用于靶向寄生虫空泡膜以外，并进入宿主细胞;然而，这个基序在输出中的确切作用是不明确的。我们使用表达嵌合蛋白的转基因恶性疟原虫来研究用于输出的PEXEL基序的功能。PEXEL构成双功能输出基序，其包含蛋白酶识别序列，所述蛋白酶识别序列在内质网中以PEXEL精氨酸和亮氨酸依赖性方式从预定用于输出的蛋白质切割。加工后，需要剩余的保守PEXEL残基将成熟蛋白导向宿主细胞。此外，我们证明，N-末端加工后的蛋白质的N乙酰化是一个PEXEL独立的过程，是不足以正确的出口到宿主细胞。这项工作定义了PEXEL中每个残基在输出到恶性疟原虫感染的红细胞中的作用。
The intracellular survival of Plasmodium falciparum within human erythrocytes is dependent on export of parasite proteins that remodel the host cell. Most exported proteins require a conserved motif (RxLxE/Q/D), termed the Plasmodium export element (PEXEL) or vacuolar targeting sequence (VTS), for targeting beyond the parasitophorous vacuole membrane and into the host cell; however, the precise role of this motif in export is poorly defined. We used transgenic P. falciparum expressing chimeric proteins to investigate the function of the PEXEL motif for export. The PEXEL constitutes a bifunctional export motif comprising a protease recognition sequence that is cleaved, in the endoplasmic reticulum, from proteins destined for export, in a PEXEL arginine- and leucine-dependent manner. Following processing, the remaining conserved PEXEL residue is required to direct the mature protein to the host cell. Furthermore, we demonstrate that N acetylation of proteins following N-terminal processing is a PEXEL-independent process that is insufficient for correct export to the host cell. This work defines the role of each residue in the PEXEL for export into the P. falciparum-infected erythrocyte.