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Identification and characterisation of a phospholipid scramblase in the malaria parasite Plasmodium falciparum
Molecular and Biochemical Parasitology ( IF 1.4 ) Pub Date : 2021-05-08 , DOI: 10.1016/j.molbiopara.2021.111374
Silvia Haase 1 , Melanie Condron 2 , David Miller 3 , Dounia Cherkaoui 1 , Sarah Jordan 1 , Jacqueline M Gulbis 4 , Jake Baum 1
Affiliation  

Recent studies highlight the emerging role of lipids as important messengers in malaria parasite biology. In an attempt to identify interacting proteins and regulators of these dynamic and versatile molecules, we hypothesised the involvement of phospholipid translocases and their substrates in the infection of the host erythrocyte by the malaria parasite Plasmodium spp. Here, using a data base searching approach of the Plasmodium Genomics Resources (www.plasmodb.org), we have identified a putative phospholipid (PL) scramblase in P. falciparum (PfPLSCR) that is conserved across the genus and in closely related unicellular algae. By reconstituting recombinant PfPLSCR into liposomes, we demonstrate metal ion dependent PL translocase activity and substrate preference, confirming PfPLSCR as a bona fide scramblase. We show that PfPLSCR is expressed during asexual and sexual parasite development, localising to different membranous compartments of the parasite throughout the intra-erythrocytic life cycle. Two different gene knockout approaches, however, suggest that PfPLSCR is not essential for erythrocyte invasion and asexual parasite development, pointing towards a possible role in other stages of the parasite life cycle.



中文翻译:


疟疾寄生虫恶性疟原虫中磷脂扰乱酶的鉴定和表征



最近的研究强调了脂质作为疟疾寄生虫生物学中重要信使的新兴作用。为了鉴定这些动态和多功能分子的相互作用蛋白和调节因子,我们假设磷脂易位酶及其底物参与了疟疾寄生虫疟原虫属对宿主红细胞的感染。在这里,使用疟原虫基因组学资源 (www.plasmodb.org) 的数据库搜索方法,我们在恶性疟原虫( Pf PLSCR) 中鉴定出了一种假定的磷脂 (PL) 混杂酶,该酶在整个属和密切相关的单细胞生物中都是保守的。藻类。通过将重组Pf PLSCR 重组到脂质体中,我们证明了金属离子依赖性 PL 转位酶活性和底物偏好,证实Pf PLSCR 是真正的扰乱酶。我们发现Pf PLSCR 在无性和有性寄生虫发育过程中表达,在整个红细胞内生命周期中定位于寄生虫的不同膜区室。然而,两种不同的基因敲除方法表明, Pf PLSCR 对于红细胞入侵和无性寄生虫发育并不是必需的,这表明 Pf PLSCR 在寄生虫生命周期的其他阶段可能发挥作用。

更新日期:2021-05-18
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