Toxoplasma F-Box Protein Regulation of the Apicoplast

弓形虫 F-Box 蛋白对顶质体的调节

• 批准号: 10539694
• 负责人: Ira J Blader
• 金额: $ 23.99万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-23 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10539694
• 关键词: Affect; Architecture; Cell Cycle; Cell Nucleus; Cell physiology; Cells; Co-Immunoprecipitations; Complex; Cullin Proteins; Data; Daughter; Defect; Drug Targeting; Enzymes; Essential Genes; Euchromatin; Eukaryota; F Box Domain; F-Box Proteins; Family; Future; Gene Expression; Genome; Goals; Growth; Histone H3; Mediating; Membrane; Metabolic; Metabolism; Microscopy; Mitotic; Organelles; Parasites; Pathway interactions; Plasmodium; Plastids; Post-Translational Protein Processing; Protein Complex Subunit; Protein Subunits; Proteins; Proteome; Regulation; Resolution; Signal Transduction; Specificity; Structure; Testing; Toxoplasma; Toxoplasma gondii; Ubiquitination; Work; candidate identification; fitness; gene product; multicatalytic endopeptidase complex; novel; pathogen; protein degradation; recruit; trafficking; ubiquitin ligase; ubiquitin-protein ligase

The SKP1/Cullin/F-box (SCF) class of E3 Ubiquitin Ligases is an evolutionarily conserved family of enzymes that regulate key cellular processes including the cell cycle, membrane trafficking, and signaling. The SCF-E3 is composed of four core components - Rbx1, Cullin1, SKP1, and a F-box protein. F-box proteins are the subunits that recruit substrate proteins to be poly-ubiquitinated by the SCF-E3, and they can also be directly poly-ubiquitinated. In previous work, we discovered that the Toxoplasma genome contains 18 predicted F-box proteins and one of these, TgFBLX2, is predicted to be the most important for fitness. We now find that TgFBLX2 is indeed important for parasite growth and in its absence inheritance of the apicoplast, a relic plastid that serves as an important metabolic hub, is reduced. We further find that TgFBLX2 localizes to a unique perinucleolar compartment. The goal of this project is to define how TgFBLX2 mediates parasite growth. In the first aim, we will determine how TgFBLX2 regulates apicoplast inheritance. In the second aim, we will characterize the perinucleolar compartment in which TgFBLX2 resides. These studies are significant because they will reveal novel interactions between the nucleus and apicoplast. In addition, these findings may be relevant to related pathogens since TgFBLX2 is conserved in Plasmodium and other apicomplexans.

SKP1/Cullin/F-box (SCF) 类 E3 泛素连接酶是一种进化型 调节关键细胞过程（包括细胞）的保守酶家族 循环、膜运输和信号传导。 SCF-E3由四个核心组成 成分 - Rbx1、Cullin1、SKP1 和 F-box 蛋白。 F-box 蛋白是 招募底物蛋白以被 SCF-E3 多泛素化的亚基，并且它们 也可以直接多聚泛素化。在之前的工作中，我们发现 弓形虫基因组包含 18 种预测的 F-box 蛋白，其中之一是 TgFBLX2， 预计对于健身来说是最重要的。我们现在发现TgFBLX2确实是 对于寄生虫的生长很重要，如果没有，则可以继承顶质体（一种遗物） 作为重要代谢中心的质体减少。我们进一步发现 TgFBLX2 定位于独特的核仁周围区室。该项目的目标是 定义 TgFBLX2 如何介导寄生虫生长。在第一个目标中，我们将确定如何 TgFBLX2 调节顶质体遗传。在第二个目标中，我们将描述 TgFBLX2 所在的核周区室。这些研究意义重大 因为它们将揭示细胞核和顶质体之间的新相互作用。在 此外，这些发现可能与相关病原体有关，因为 TgFBLX2 是 在疟原虫和其他顶复菌中保守。