An exported protein-interacting complex involved in the trafficking of virulence determinants in Plasmodium-infected erythrocytes.
An exported protein-interacting complex involved in the trafficking of virulence determinants in Plasmodium-infected erythrocytes.
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DOI：
10.1038/ncomms16044
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发表时间：
2017-07-10
影响因子：
16.6
通讯作者：
Tilley L
中科院分区：
文献类型：
--
作者：
Batinovic S;McHugh E;Chisholm SA;Matthews K;Liu B;Dumont L;Charnaud SC;Schneider MP;Gilson PR;de Koning-Ward TF;Dixon MWA;Tilley L
恶性疟原虫红细胞膜蛋白1(PfEMP1)是恶性疟原虫红细胞膜蛋白1(PfEMP1)的主要成分。在这里，我们研究了PfEMP1交易中间体在受感染的红细胞中的物理组织，并使用表位标记的最小结构(PfEMP1B)确定了相互作用的伙伴。我们发现定位于寄生虫空泡(PV)的PfEMP1B与PTEX(出口蛋白转运子)的组件以及一种新的蛋白质复合体EPIC(出口蛋白相互作用复合体)相互作用。在RBC细胞质内，PfEMP1B与毛雷氏裂隙成分和RBC伴侣复合体相互作用。我们定义了史诗般的相互作用组，并使用可诱导的敲除方法表明，它的一个组成部分，寄生虫空泡蛋白-1(PV1)的耗尽，会导致节状结构改变，细胞刚性降低，与CD36的结合减少。因此，我们表明，伯氏疟原虫PV1同源物的缺失与体内寄生虫毒力的减弱有关。被疟原虫感染的红细胞将毒力因子，如PfEMP1，输出到细胞表面。在这里，作者发现了一种名为EPIC的蛋白质复合体，它在出口过程中与PfEMP1相互作用，他们表明，EPIC组分的敲除会影响寄生虫的毒力。
The malaria parasite, Plasmodium falciparum, displays the P. falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of infected red blood cells (RBCs). We here examine the physical organization of PfEMP1 trafficking intermediates in infected RBCs and determine interacting partners using an epitope-tagged minimal construct (PfEMP1B). We show that parasitophorous vacuole (PV)-located PfEMP1B interacts with components of the PTEX (Plasmodium Translocon of EXported proteins) as well as a novel protein complex, EPIC (Exported Protein-Interacting Complex). Within the RBC cytoplasm PfEMP1B interacts with components of the Maurer’s clefts and the RBC chaperonin complex. We define the EPIC interactome and, using an inducible knockdown approach, show that depletion of one of its components, the parasitophorous vacuolar protein-1 (PV1), results in altered knob morphology, reduced cell rigidity and decreased binding to CD36. Accordingly, we show that deletion of the Plasmodium berghei homologue of PV1 is associated with attenuation of parasite virulence in vivo. Plasmodium-infected red blood cells export virulence factors, such as PfEMP1, to the cell surface. Here, the authors identify a protein complex termed EPIC that interacts with PfEMP1 during export, and they show that knockdown of an EPIC component affects parasite virulence.
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影响因子：
16.6
作者：
De Niz M;Ullrich AK;Heiber A;Blancke Soares A;Pick C;Lyck R;Keller D;Kaiser G;Prado M;Flemming S;Del Portillo H;Janse CJ;Heussler V;Spielmann T
通讯作者：
Spielmann T
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：
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：
3.4
作者：
Guizetti J;Scherf A
通讯作者：
Scherf A
影响因子：
64.8
作者：
Beck, Josh R.;Muralidharan, Vasant;Oksman, Anna;Goldberg, Daniel E.
通讯作者：
Goldberg, Daniel E.