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迈向对顶复门肌动蛋白运动的分子理解:通往疟疾治疗新靶点之路?

Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?

作者信息

Kumpula Esa Pekka, Kursula Inari

机构信息

Faculty of Biochemistry and Molecular Medicine, University of Oulu, PO Box 3000, 90014 Oulu, Finland.

出版信息

Acta Crystallogr F Struct Biol Commun. 2015 May;71(Pt 5):500-13. doi: 10.1107/S2053230X1500391X. Epub 2015 Apr 16.

Abstract

Apicomplexan parasites are the causative agents of notorious human and animal diseases that give rise to considerable human suffering and economic losses worldwide. The most prominent parasites of this phylum are the malaria-causing Plasmodium species, which are widespread in tropical and subtropical regions, and Toxoplasma gondii, which infects one third of the world's population. These parasites share a common form of gliding motility which relies on an actin-myosin motor. The components of this motor and the actin-regulatory proteins in Apicomplexa have unique features compared with all other eukaryotes. This, together with the crucial roles of these proteins, makes them attractive targets for structure-based drug design. In recent years, several structures of glideosome components, in particular of actins and actin regulators from apicomplexan parasites, have been determined, which will hopefully soon allow the creation of a complete molecular picture of the parasite actin-myosin motor and its regulatory machinery. Here, current knowledge of the function of this motor is reviewed from a structural perspective.

摘要

顶复门寄生虫是导致人类和动物患恶名昭著疾病的病原体,在全球范围内造成了巨大的人类痛苦和经济损失。该门中最著名的寄生虫是导致疟疾的疟原虫属物种,广泛分布于热带和亚热带地区,以及感染全球三分之一人口的弓形虫。这些寄生虫具有一种共同的滑行运动形式,依赖于肌动蛋白-肌球蛋白马达。与所有其他真核生物相比,这种马达的组成成分以及顶复门中的肌动蛋白调节蛋白具有独特的特征。这一点,再加上这些蛋白质的关键作用,使其成为基于结构的药物设计的有吸引力的靶点。近年来,已经确定了一些滑行体成分的结构,特别是来自顶复门寄生虫的肌动蛋白和肌动蛋白调节蛋白的结构,有望很快构建出寄生虫肌动蛋白-肌球蛋白马达及其调节机制的完整分子图谱。在此,从结构角度对该马达功能的当前知识进行综述。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9651/4427158/1cfe7ce8af7c/f-71-00500-fig1.jpg

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