A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites
A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites
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DOI：
10.1074/jbc.m509807200
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发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
Cowman, AF
中科院分区：
文献类型：
--
作者：
Baum, J;Richard, D;Cowman, AF
Apicomplexan寄生虫构成了感染人和动物的最重要的病原体之一。疟原虫属的肝阶段孢子岩。弓形虫弓形虫（分别是疟疾和弓形虫病的致病药物）的tachyzoites使用称为滑动运动的独特运动模式来侵入宿主细胞和跨细胞底物。这种类似变形虫的运动使用了与血小板素相关的匿名蛋白（TRAP）家族的寄生虫粘附蛋白，以及通过肌动蛋白膜蛋白运动与内膜内膜复合物通过肌动蛋白 - 肌球蛋白运动的一组将细胞外粘附素连接起来的蛋白质。然而，疟原虫血液阶段的蛋白石并未表现出滑动运动。在这里，我们表明，构成运动复合物的关键蛋白的同源物，包括最近鉴定出的Glideosom相关蛋白45和50（GAP40和GAP50）（falciparum P. merozoites中），并且似乎在红细胞入侵中起作用。此外，我们确定了一个梅罗佐伊特陷阱同源物，称为MTRAP，一种微生物蛋白，它与陷阱共享关键特征，包括血小板传播重复域，推定的rhomboid-----------骨骼裂解位点和细胞质的尾巴，该尾巴在体内结合了actin racting actin racting actin linging actin linging actin racting actin racting actin racting cinting actin racting cinting actin racting racting cinting actin racting cinting actin racting cinting actin racting cinting actin racting cinting actin的结合。蛋白醛酶。对其他寄生虫基因组的分析表明，该运动络合物的成分在不同的Apicomplexan属中保守。电动机复合物的保护表明，一种常见的分子机制是所有Apicomplexan运动的基础，鉴于其独特的特性，它突出了许多用于治疗人类和牲畜主要疾病的药物干预措施的新靶标。
Apicomplexan parasites constitute one of the most significant groups of pathogens infecting humans and animals. The liver stage sporozoites of Plasmodium spp. and tachyzoites of Toxoplasma gondii, the causative agents of malaria and toxoplasmosis, respectively, use a unique mode of locomotion termed gliding motility to invade host cells and cross cell substrates. This amoeboid-like movement uses a parasite adhesin from the thrombospondin-related anonymous protein (TRAP) family and a set of proteins linking the extracellular adhesin, via an actin-myosin motor, to the inner membrane complex. The Plasmodium blood stage merozoite, however, does not exhibit gliding motility. Here we show that homologues of the key proteins that make up the motor complex, including the recently identified glideosome-associated proteins 45 and 50 (GAP40 and GAP50), are present in P. falciparum merozoites and appear to function in erythrocyte invasion. Furthermore, we identify a merozoite TRAP homologue, termed MTRAP, a micronemal protein that shares key features with TRAP, including a thrombospondin repeat domain, a putative rhomboid-protease cleavage site, and a cytoplasmic tail that, in vitro, binds the actin-binding protein aldolase. Analysis of other parasite genomes shows that the components of this motor complex are conserved across diverse Apicomplexan genera. Conservation of the motor complex suggests that a common molecular mechanism underlies all Apicomplexan motility, which, given its unique properties, highlights a number of novel targets for drug intervention to treat major diseases of humans and livestock.