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

顶复门寄生虫中肌球蛋白马达的作用模式

• 批准号: 5175722
• 负责人: Professorin Dr. Dominique Soldati-Favre, Ph.D.
• 金额: --
• 依托单位: Départment de Microbiologie et Medecine Moleculaire
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1999
• 资助国家: 德国
• 起止时间: 1998-12-31 至 2001-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5175722?language=en
• 关键词: Mode; action; myosin; motors; Apicomplexa

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.

顶复门的原生动物寄生虫具有巨大的医学和兽医意义，是造成多种疾病的原因，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。宿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。弓形虫是最普遍存在的顶复门，它具有主动穿透几乎所有温血动物的任何有核细胞的非凡能力。导致这种非凡的入侵成功的机制尚未在分子水平上得到阐明。与其他顶复门一样，弓形虫缺乏用于运动的纤毛或鞭毛，但具有一种不寻常的滑行运动形式，这对于宿主细胞的入侵至关重要。滑行运动的基本引擎是肌动蛋白细胞骨架，并且可能涉及肌球蛋白以沿着肌动蛋白丝产生机械化学力。迄今为止在 Apicomplexa 中鉴定的所有肌球蛋白都非常非常规，并构成了一种新的系统发育和结构类别的肌球蛋白 (XIV)。本研究计划的主要目标是表征顶复门寄生虫滑行运动中涉及的肌球蛋白并确定其作用模式。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。