Plasmodium falciparum OTU-like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8
Plasmodium falciparum OTU-like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8
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DOI：
10.1111/cmi.12748
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发表时间：
2017-09-01
影响因子：
3.4
通讯作者：
Mohmmed, Asif
中科院分区：
文献类型：
--
作者：
Datta, Gaurav;Hossain, Mohammad E.;Mohmmed, Asif
原核生物疟原虫的两种寄生虫细胞器--顶质体和顶质体的代谢途径被认为是合适的药物靶点。在本研究中，我们已经确定了一种新的卵巢肿瘤单位（OTU）结构域含有半胱氨酸蛋白酶的恶性疟原虫（PfOTU）的功能作用。天然蛋白质上的C-末端可调节的荧光亲和标签用于其定位和功能表征。详细的研究表明PfOTU的囊泡定位及其与顶质体的关联。降解标签介导的PfOTU敲低导致顶质体发育异常，并在随后的细胞周期中阻断寄生虫发育超过早期阶段; PfOTU的下调阻碍顶质体蛋白质的输入。此外，类异戊二烯受体介导的寄生虫生长拯救实验证实PfOTU敲低特异性影响功能性顶质体的发育。我们还提供了PfOTU在Atg 8的膜去缀合中可能的生物学功能的证据，这可能与顶质体蛋白质输入有关。总体而言，我们的研究结果表明，PfOTU参与顶质体稳态，并与Atg 8在维持寄生虫顶质体中的非经典功能相关。
The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel ovarian tumour unit (OTU) domain-containing cysteine protease of Plasmodium falciparum (PfOTU). A C-terminal regulatable fluorescent affinity tag on native protein was utilised for its localization and functional characterization. Detailed studies showed vesicular localization of PfOTU and its association with the apicoplast. Degradationtag mediated knockdown of PfOTU resulted in abnormal apicoplast development and blocked development of parasites beyond early-schizont stages in subsequent cell cycle; downregulation of PfOTU hindered apicoplast protein import. Further, the isoprenoid precursor-mediated parasite growth-rescue experiments confirmed that PfOTU knockdown specifically effect development of functional apicoplast. We also provide evidence for a possible biological function of PfOTU in membrane deconjugation of Atg8, which may be linked with the apicoplast protein import. Overall, our results show that the PfOTU is involved in apicoplast homeostasis and associates with the noncanonical function of Atg8 in maintenance of parasite apicoplast.