Cooperative domains define a unique host cell-targeting signal in Plasmodium falciparum-infected erythrocytes
Cooperative domains define a unique host cell-targeting signal in Plasmodium falciparum-infected erythrocytes
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DOI：
10.1073/pnas.2133080100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Haldar, K
中科院分区：
文献类型：
--
作者：
Lopez-Estraño, C;Bhattacharjee, S;Haldar, K
当恶性疟原虫感染红细胞时，它会驻留在一个寄生虫空泡中，并将蛋白质显著地输出到宿主细胞的外周。这些蛋白质中的两种，富含组氨酸的蛋白质I和II（PfHRPI和PfHRPII），被输出到红细胞胞质。PfHRPI与介导脑型疟疾的细胞表面“多节”突起有关，是一种常见的死亡原因。PfHRPII与（i）疟原虫色素（与疾病相关的黑色色素）的产生以及（ii）与红细胞细胞骨架的相互作用有关。在这里，我们表明，一个三方的信号，这是由一个内质网型的信号序列，然后由一个双向液泡易位信号来自HRPII和HRIPI出口GFP从寄生虫液泡到宿主细胞质。二分液泡易位信号由独特的肽（约40个氨基酸）序列组成。其内部的结构域包含用于输出到宿主红细胞中的“裂缝”运输中间体的信号，并且因此可以调节输出到宿主细胞质的途径。翻译后，空泡出口的蛋白质的信号迄今尚未被描述在真核分泌。
When the malaria parasite Plasmodium falciparum infects an erythrocyte, it resides in a parasitophorous vacuole and remarkably exports proteins into the periphery of its host cell. Two of these proteins, the histidine-rich proteins I and II (PfHRPI and PfHRPII), are exported to the erythrocyte cytoplasm. PfHRPI has been linked to cell-surface "knobby" protrusions that mediate cerebral malaria and are a frequent cause of death. PfHRPII has been implicated in (i) the production of hemozoin, the black pigment associated with disease, as well as (ii) interactions with the erythrocyte cytoskeleton. Here we show that a tripartite signal that is comprised of an endoplasmic reticulum-type signal sequence followed by a bipartite vacuolar translocation signal derived from HRPII and HRIPI exports GFP from the parasitophorous vacuole to the host cytoplasm. The bipartite vacuolar translocation signal is comprised of unique, peptidic (approximate to40-aa) sequences. A domain within it contains the signal for export to "cleft" transport intermediates in the host erythrocyte and may thereby regulate the pathway of export to the host cytoplasm. A signal for posttranslational, vacuolar exit of proteins has hitherto not been described in eukaryotic secretion.