Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export.
Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export.
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新PNEP的识别表明，在恶性疟原虫蛋白蛋白质出口中，非二氧醇的大量导出和基础。
DOI：
10.1371/journal.ppat.1003546
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Spielmann T
中科院分区：
文献类型：
--
作者：
Heiber A;Kruse F;Pick C;Grüring C;Flemming S;Oberli A;Schoeler H;Retzlaff S;Mesén-Ramírez P;Hiss JA;Kadekoppala M;Hecht L;Holder AA;Gilberger TW;Spielmann T
疟疾血液阶段寄生虫将大量蛋白质输出到其宿主红细胞中，以将其从主要为血红蛋白的容器改变为用于运输氧气的容器，进入寄生虫繁殖的生态位。为了理解这一过程，关键是要知道哪些寄生虫蛋白质被输出到宿主细胞中。这是由PEXEL/HT序列，在许多出口蛋白质中发现的五个残基的基序，导致预测的exportome的帮助。然而，几种PEXEL/HT阴性输出蛋白（PNEP）表明该输出组是不完整的，并且仍然不知道是否存在以及存在多少其他PNEP。在这里，我们报告的最致命的疟疾寄生虫恶性疟原虫新的PNEPs的鉴定。这包括具有偏离先前已知PNEP的结构域结构的蛋白质，并表明PNEP不是罕见的例外。出乎意料的是，这包括MSP-7相关蛋白（MSRP）家族的成员，表明MSRP的意外功能。分析区域介导出口选定的新PNEPs，我们表明，前20个氨基酸的PNEPs没有一个经典的N-末端信号肽足以促进出口的报告，确认这是一个共享的属性的概念，所有PNEPs的这种类型。此外，我们利用新发现的可溶性PNEPs表明，这种类型的出口蛋白需要展开移动从寄生虫液泡（PV）进入宿主细胞。这表明可溶性PNEP（如PEXEL/HT蛋白）通过跨PV膜（PVM）移位而输出，强调寄生虫外周的蛋白质移位是疟疾寄生虫蛋白质输出的一般方式。疟疾寄生虫在红细胞内繁殖，红细胞是高度特化的细胞，需要深刻的改变来支持寄生虫生存。为了了解寄生虫是如何接管宿主细胞的，有必要知道它的分子工具箱来执行这一过程，其中包括从寄生虫输出到宿主细胞的蛋白质。虽然许多这样的蛋白质是已知的，因为它们含有明确定义的PEXEL/HT基序，但未知数量的其他蛋白质缺乏这样的基序。在这里，我们提出了几个这些PEXEL负输出蛋白（PNEPs）的鉴定。我们分析了这些蛋白质的一个子集中介导出口的序列，发现在缺乏N-末端信号肽的PNEP中，这些蛋白质的N-末端区域足以介导出口。因此，尽管缺乏明确的特征序列，但这些区域共享介导输出的属性。此外，我们发现的证据表明，可溶性PNEPs被转运到宿主细胞通过易位跨寄生虫膜周围的寄生虫。这增加了另一组蛋白质来共享这种特性，并突出了蛋白质易位作为迄今为止测试的所有类型的疟疾蛋白质的一般输出方式。
Malaria blood stage parasites export a large number of proteins into their host erythrocyte to change it from a container of predominantly hemoglobin optimized for the transport of oxygen into a niche for parasite propagation. To understand this process, it is crucial to know which parasite proteins are exported into the host cell. This has been aided by the PEXEL/HT sequence, a five-residue motif found in many exported proteins, leading to the prediction of the exportome. However, several PEXEL/HT negative exported proteins (PNEPs) indicate that this exportome is incomplete and it remains unknown if and how many further PNEPs exist. Here we report the identification of new PNEPs in the most virulent malaria parasite Plasmodium falciparum. This includes proteins with a domain structure deviating from previously known PNEPs and indicates that PNEPs are not a rare exception. Unexpectedly, this included members of the MSP-7 related protein (MSRP) family, suggesting unanticipated functions of MSRPs. Analyzing regions mediating export of selected new PNEPs, we show that the first 20 amino acids of PNEPs without a classical N-terminal signal peptide are sufficient to promote export of a reporter, confirming the concept that this is a shared property of all PNEPs of this type. Moreover, we took advantage of newly found soluble PNEPs to show that this type of exported protein requires unfolding to move from the parasitophorous vacuole (PV) into the host cell. This indicates that soluble PNEPs, like PEXEL/HT proteins, are exported by translocation across the PV membrane (PVM), highlighting protein translocation in the parasite periphery as a general means in protein export of malaria parasites. Malaria parasites multiply within erythrocytes, highly specialized cells that require profound alterations to support parasite survival. In order to understand how the parasite takes over the host cell it is necessary to know its molecular toolbox to carry out this process, which consists of the proteins exported from the parasite into the host cell. While many such proteins are known because they contain the clearly defined PEXEL/HT motif, an unknown number of further proteins lack such a motif. Here we present the identification of several of these PEXEL negative exported proteins (PNEPs). We analyzed the sequences mediating export in a subset of these proteins and find that in PNEPs lacking an N-terminal signal peptide, the N-terminal region of these proteins is sufficient to mediate export. Thus, despite the lack of a clear signature sequence, these regions share a property mediating export. In addition, we found evidence that suggests that soluble PNEPs get transported into the host cell by translocation across the parasitophorous membrane that surrounds the parasite. This adds a further group of proteins to share this property and highlights protein translocation as a general means of export in all types of malaria proteins tested so far.
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影响因子：
3.6
作者：
Dixon, Matthew W. A.;Kenny, Shannon;Tilley, Leann
通讯作者：
Tilley, Leann
影响因子：
--
作者：
Kadekoppala, Madhusudan;Ogun, Solabomi A.;Holder, Anthony A.
通讯作者：
Holder, Anthony A.
影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
64.8
作者：
de Koning-Ward, Tania F.;Gilson, Paul R.;Boddey, Justin A.;Rug, Melanie;Smith, Brian J.;Papenfuss, Anthony T.;Sanders, Paul R.;Lundie, Rachel J.;Maier, Alexander G.;Cowman, Alan F.;Crabb, Brendan S.
通讯作者：
Crabb, Brendan S.
影响因子：
3.6
作者：
Hanssen, Eric;Hawthorne, Paula;Tilley, Leann
通讯作者：
Tilley, Leann