Functional characterization of the main integral protein components of the parasite-host cell interface of Plasmodium falciparum blood stages
恶性疟原虫血液阶段寄生虫-宿主细胞界面主要整合蛋白成分的功能表征
基本信息
- 批准号:404870441
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2018
- 资助国家:德国
- 起止时间:2017-12-31 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The intracellular development of the human malaria parasite Plasmodium falciparum in red blood cells is responsible for the clinical symptoms of malaria. In the red blood cell, the parasite is separated from the host cell cytosol by a membrane called the parasitophorous vacuolar membrane (PVM). This membrane plays a key role in the interaction of the parasite with its host cell but many of its functions are poorly understood or unknown. The PVM contains short, highly charged and highly abundant integral membrane proteins termed EXP1 and ETRAMPs (a family of 14 proteins). These molecules are the only so far known proteins bridging this membrane (they contain a domain reaching into the host cell and one facing the parasite). Several, including EXP1, are indicated to be essential for parasite survival and they likely play critical roles in the interaction of the parasite with the host cell. However, due to technical limitations, they have so far not been functionally analysed in P. falciparum parasites. Using new technology we generated a conditional knock out of EXP1. Here we propose to use this to study EXP1 and use the same technology to functionally analyse ETRAMPs. In addition we developed a new modified proximity biotinylation method to identify interaction partners and compartment proteomes that we propose to use to identify factors interacting with the host cell facing domain of EXP1 and ETRAMPs. This will also generate a proteome of the outer face of the PVM that with other means is difficult to obtain. We expect this work to unravel the function of the major integral components of the parasite host cell interface and to contribute to an understanding how the parasite exploits and interacts with the host red blood cell.
人类疟疾寄生虫恶性疟原虫在红细胞内的细胞内发育是导致疟疾临床症状的原因。在红细胞中,寄生虫与宿主细胞胞浆之间被一种称为寄生虫的液泡膜(PVM)隔开。这一膜在寄生虫与宿主细胞的相互作用中起着关键作用,但它的许多功能却鲜为人知或未知。PVM含有短小、高电荷和高度丰富的完整膜蛋白,称为EXP1和ETRAMPs(一个14种蛋白质家族)。到目前为止,这些分子是唯一已知的连接这一膜的蛋白质(它们包含一个到达宿主细胞的区域和一个面对寄生虫的区域)。包括EXP1在内的几个基因被认为是寄生虫生存所必需的,它们可能在寄生虫与宿主细胞的相互作用中发挥关键作用。然而,由于技术的限制,到目前为止还没有在恶性疟原虫中对它们进行功能分析。使用新技术,我们产生了EXP1的条件敲除。在这里,我们建议利用这一点来研究EXP1,并使用相同的技术来从功能上分析ETRAMP。此外,我们开发了一种新的改进的邻近生物素化方法来识别相互作用伙伴和隔室蛋白质组,我们建议使用该方法来识别与宿主细胞面对的EXP1和ETRAMPs结构域相互作用的因子。这也将产生PVM外表面的蛋白质组,这是用其他方法很难获得的。我们希望这项工作将揭开寄生虫宿主细胞界面主要组成部分的功能,并有助于了解寄生虫如何利用宿主红细胞并与之相互作用。
项目成果
期刊论文数量(0)
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Dr. Tobias Spielmann其他文献
Dr. Tobias Spielmann的其他文献
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{{ truncateString('Dr. Tobias Spielmann', 18)}}的其他基金
Characterisation of the vacuolar compartment of malaria parasites within human red blood cells
人红细胞内疟疾寄生虫液泡室的表征
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261022028 - 财政年份:2014
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Export determinants and pathways in protein trafficking in the human malaria parasite Plasmodium falciparum
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65594974 - 财政年份:2008
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