Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.
School of Medicine, Deakin University, Waurn Ponds, Victoria 3220, Australia.
Nat Commun. 2017 Jul 10;8:16044. doi: 10.1038/ncomms16044.
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.
疟原虫，恶性疟原虫，在感染的红细胞（RBC）表面显示出恶性疟原虫红细胞膜蛋白 1（PfEMP1）。我们在这里检查了 PfEMP1 运输中间产物在感染的 RBC 中的物理组织，并使用表位标记的最小构建体（PfEMP1B）确定相互作用的伙伴。我们表明，寄生空泡（PV）定位的 PfEMP1B 与 PTEX（出口蛋白的疟原虫转位）的成分以及一个新的蛋白质复合物 EPIC（Exported Protein-Interacting Complex）相互作用。在 RBC 细胞质中，PfEMP1B 与 Maurer 裂隙和 RBC 伴侣蛋白复合物的成分相互作用。我们定义了 EPIC 相互作用组，并使用诱导性敲低方法表明，其成分之一，寄生空泡蛋白-1（PV1）的耗竭导致旋钮形态改变、细胞刚性降低和与 CD36 的结合减少。因此，我们表明，缺失 PV1 的疟原虫伯氏疟原虫同源物与寄生虫在体内毒力的衰减有关。
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