Haase Silvia, Cabrera Ana, Langer Christine, Treeck Moritz, Struck Nicole, Herrmann Susann, Jansen Pascal W, Bruchhaus Iris, Bachmann Anna, Dias Suzana, Cowman Alan F, Stunnenberg Hendrik G, Spielmann Tobias, Gilberger Tim-Wolf
Research Group Malaria II, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359 Hamburg, Germany.
Infect Immun. 2008 Mar;76(3):879-87. doi: 10.1128/IAI.00144-07. Epub 2008 Jan 3.
One of the key processes in the pathobiology of the malaria parasite is the invasion and subsequent modification of the human erythrocyte. In this complex process, an unknown number of parasite proteins are involved, some of which are leading vaccine candidates. The majority of the proteins that play pivotal roles in invasion are either stored in the apical secretory organelles or located on the surface of the merozoite, the invasive stage of the parasite. Using transcriptional and structural features of these known proteins, we performed a genomewide search that identified 49 hypothetical proteins with a high probability of being located on the surface of the merozoite or in the secretory organelles. Of these candidates, we characterized a novel leucine zipper-like protein in Plasmodium falciparum that is conserved in Plasmodium spp. This protein is expressed in late blood stages and localizes to the rhoptries of the parasite. We demonstrate that this Plasmodium sp.-specific protein has a high degree of conservation within field isolates and that it is refractory to gene knockout attempts and thus might play an important role in invasion.
疟原虫病理生物学的关键过程之一是对人类红细胞的入侵及随后的修饰。在这个复杂的过程中，涉及数量不明的寄生虫蛋白，其中一些是主要的疫苗候选物。在入侵过程中起关键作用的大多数蛋白质要么储存在顶端分泌细胞器中，要么位于裂殖子（寄生虫的入侵阶段）表面。利用这些已知蛋白质的转录和结构特征，我们进行了全基因组搜索，鉴定出49种假设蛋白质，它们极有可能位于裂殖子表面或分泌细胞器中。在这些候选物中，我们鉴定出一种恶性疟原虫中新型的亮氨酸拉链样蛋白，该蛋白在疟原虫属中保守。这种蛋白质在血液后期阶段表达，并定位于寄生虫的棒状体。我们证明，这种疟原虫属特异性蛋白在野外分离株中具有高度保守性，并且难以通过基因敲除实验进行研究，因此可能在入侵过程中发挥重要作用。
