The Exported Protein PbCP1 Localises to Cleft-Like Structures in the Rodent Malaria Parasite Plasmodium berghei
The Exported Protein PbCP1 Localises to Cleft-Like Structures in the Rodent Malaria Parasite Plasmodium berghei
复制标题
输出蛋白 PbCP1 定位于啮齿类疟原虫伯氏疟原虫的裂口状结构
作者：
Silvia Haase;E. Hanssen;Kathryn M. Matthews;M. Kalanon;T. D. de Koning
蛋白质输出到宿主红细胞中是恶性疟原虫的病理生物学中的关键过程之一，其广泛重塑红细胞以确保其毒力和存活。在这项研究中，我们的目的是进一步阐明啮齿动物疟原虫伯氏疟原虫中的蛋白质输出机制，并进一步证明疟原虫属中宿主细胞重塑的保守性。基于一个被称为PEXEL（疟原虫输出元件）的输出基序（R/KxLxE/Q/D）的存在，我们已经产生了转基因伯氏疟原虫寄生虫系，其表达了疟原虫输出蛋白的GFP嵌合体，并详细分析了一种新鉴定的输出蛋白。这种被称为PbCP 1（伯氏疟原虫裂缝样蛋白1）的必需蛋白含有非典型的PEXEL基序（RxLxY），并进一步以蛋白质C末端的两个预测跨膜结构域（2 TMD）为特征。我们已经在功能上验证了不寻常的PEXEL基序在PbCP 1和分析的作用，2 TMD区域，这是需要招聘PbCP 1离散膜结构在红细胞胞质中，有一个回旋，囊泡管状形态的电子显微镜。重要的是，这项研究表明，啮齿类疟疾物种也会诱导其宿主红细胞发生变化。
Protein export into the host red blood cell is one of the key processes in the pathobiology of the malaria parasite Plasmodiumtrl falciparum, which extensively remodels the red blood cell to ensure its virulence and survival. In this study, we aimed to shed further light on the protein export mechanisms in the rodent malaria parasite P. berghei and provide further proof of the conserved nature of host cell remodeling in Plasmodium spp. Based on the presence of an export motif (R/KxLxE/Q/D) termed PEXEL (Plasmodium export element), we have generated transgenic P. berghei parasite lines expressing GFP chimera of putatively exported proteins and analysed one of the newly identified exported proteins in detail. This essential protein, termed PbCP1 (P. berghei Cleft-like Protein 1), harbours an atypical PEXEL motif (RxLxY) and is further characterised by two predicted transmembrane domains (2TMD) in the C-terminal end of the protein. We have functionally validated the unusual PEXEL motif in PbCP1 and analysed the role of the 2TMD region, which is required to recruit PbCP1 to discrete membranous structures in the red blood cell cytosol that have a convoluted, vesico-tubular morphology by electron microscopy. Importantly, this study reveals that rodent malaria species also induce modifications to their host red blood cell.