Mode of action of myosin motors in Apicomplexa parasites (Funktionsweise des Aktinomyosinmotors von Apicomplexen Parasiten)

尖端复合门的原生动物寄生虫具有巨大的医学和兽医学意义，导致多种疾病，包括疟疾、弓形虫病、球虫病、隐孢子虫病、泰勒虫病和巴贝斯虫病。寄主细胞的成功附着和入侵是这些专性细胞内寄生虫生存的关键。弓形虫是尖端复合体中最普遍的一种，它已经发展出一种非凡的能力，可以主动穿透几乎所有温血动物的任何有核细胞。导致这种特殊的入侵成功的机制目前还没有在分子水平上阐明。像其他复合体弓形虫一样，弓形虫没有纤毛或鞭毛来移动，但有一种不寻常的滑行运动形式，这是宿主细胞入侵所必需的。滑动运动的基本引擎是肌动蛋白细胞骨架，很可能涉及肌球蛋白产生沿肌动蛋白细丝的机械力化学力。到目前为止，在Apicomplexa中发现的所有肌球蛋白都是非常非常规的，构成了一个新的肌球蛋白系统发育和结构类别(XIV)。这项研究计划的主要目的是描述参与Apicomplexan寄生虫滑动运动的肌球蛋白(S)，并确定它们的作用方式。为了实现这一目标，我们将结合体外和体内研究来阐明它们的结构/功能关系。

Protozoan parasites of the phylum Apicomplexa are of enormous medical and veterinary significance, being responsible for a wide variety of diseases including malaria, toxoplasmosis, coccidiosis, cryptosporidiosis, theileriosis and babesiosis. Successful attachment and invasion of the host cells are key to the survival of these obligate intracellular parasites. Toxoplasma gondii, the most ubiquitous of the Apicomplexan, has developed a remarkable ability to actively penetrate any nucleated cells from virtually all warm blooded animals. The mechanisms responsible for this exceptional success in invasion are not elucidated yet at the molecular level. Like other Apicomplexan, T. gondii lacks cilia or flagella for locomotion but harbors an unusual form of gliding motility which is essential for host cell invasion. The basic engine for gliding locomotion is the actin cytoskeleton and likely involves a myosin to generate the mechanochemical force along the actin filaments. All myosins identified so far in Apicomplexa are very unconventional and constitute a novel phylogenetic and structural class of myosins (XIV). The main goal of this research proposal is to characterize the myosin(s) involved in the gliding motility of Apicomplexan parasites and to determine their mode of action. To achieve this goal we will combine in vitro and in vivo studies to elucidate their structure/function relationships.