Gene-by-gene screen of the unknown proteins encoded on Plasmodium falciparum chromosome 3.

IF 9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Systems Pub Date : 2023-01-18 DOI:10.1016/j.cels.2022.12.001
Jessica Kimmel, Marius Schmitt, Alexej Sinner, Pascal Wilhelmus Theodorus Christianus Jansen, Sheila Mainye, Gala Ramón-Zamorano, Christa Geeke Toenhake, Jan Stephan Wichers-Misterek, Jakob Cronshagen, Ricarda Sabitzki, Paolo Mesén-Ramírez, Hannah Michaela Behrens, Richárd Bártfai, Tobias Spielmann
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引用次数: 6

Abstract

Taxon-specific proteins are key determinants defining the biology of all organisms and represent prime drug targets in pathogens. However, lacking comparability with proteins in other lineages makes them particularly difficult to study. In malaria parasites, this is exacerbated by technical limitations. Here, we analyzed the cellular location, essentiality, function, and, in selected cases, interactome of all unknown non-secretory proteins encoded on an entire P. falciparum chromosome. The nucleus was the most common localization, indicating that it is a hotspot of parasite-specific biology. More in-depth functional studies with four proteins revealed essential roles in DNA replication and mitosis. The mitosis proteins defined a possible orphan complex and a highly diverged complex needed for spindle-kinetochore connection. Structure-function comparisons indicated that the taxon-specific proteins evolved by different mechanisms. This work demonstrates the feasibility of gene-by-gene screens to elucidate the biology of malaria parasites and reveal critical parasite-specific processes of interest as drug targets.

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恶性疟原虫3号染色体未知编码蛋白的逐基因筛选。
分类群特异性蛋白是定义所有生物体生物学的关键决定因素,并代表病原体的主要药物靶点。然而,由于缺乏与其他谱系中蛋白质的可比性,使得它们特别难以研究。在疟疾寄生虫方面,技术限制加剧了这种情况。在这里,我们分析了细胞的位置,必要性,功能,并在选定的情况下,所有未知的非分泌蛋白编码在整个恶性疟原虫染色体的相互作用。细胞核是最常见的定位,表明它是寄生虫特异性生物学的热点。更深入的功能研究揭示了四种蛋白质在DNA复制和有丝分裂中的重要作用。有丝分裂蛋白定义了一种可能的孤儿复合体和纺锤体-着丝点连接所需的高度分化复合体。结构-功能比较表明,分类群特异性蛋白的进化机制不同。这项工作证明了基因筛选的可行性,以阐明疟疾寄生虫的生物学和揭示关键的寄生虫特异性过程感兴趣的药物靶点。
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来源期刊
Cell Systems
Cell Systems Medicine-Pathology and Forensic Medicine
CiteScore
16.50
自引率
1.10%
发文量
84
审稿时长
42 days
期刊介绍: In 2015, Cell Systems was founded as a platform within Cell Press to showcase innovative research in systems biology. Our primary goal is to investigate complex biological phenomena that cannot be simply explained by basic mathematical principles. While the physical sciences have long successfully tackled such challenges, we have discovered that our most impactful publications often employ quantitative, inference-based methodologies borrowed from the fields of physics, engineering, mathematics, and computer science. We are committed to providing a home for elegant research that addresses fundamental questions in systems biology.
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