Toxoplasma F-Box Protein Regulation of the Apicoplast

弓形虫 F-Box 蛋白对顶质体的调节

基本信息

批准号：
10626164
负责人：
Ira J Blader
金额：
$ 20.05万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-23 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10626164
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 Mitotic Nucleolar Proteins Organelles Parasites Pathway interactions Plasmodium Plastids Post-Translational Protein Processing Protein Complex Subunit Protein Subunits Proteins Proteome Regulation Signal Transduction Skp1-Cullin-F-Box Proteins Specificity Structure Testing Toxoplasma Toxoplasma gondii Ubiquitination Work candidate identification fitness gene product multicatalytic endopeptidase complex novel pathogen protein degradation recruit segregation superresolution microscopy trafficking ubiquitin ligase ubiquitin-protein ligase

项目摘要

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.

E3泛素连接酶的SKP1/cullin/f-box（SCF）类是进化保守的酶家族，调节包括细胞在内的关键细胞过程循环，膜运输和信号传导。 SCF-E3由四个核心组成组件-RBX1，Cullin1，SKP1和F -box蛋白。 F-box蛋白是募集底物蛋白的亚基是由SCF-E3衍生的，它们是也可以直接泛素化。在以前的工作中，我们发现弓形虫基因组包含18种预测的F-box蛋白，其中一种是TGFBLX2，预计将是健身最重要的。我们现在发现TGFBLX2确实是对于寄生虫的生长以及其缺乏植物的遗传而重要的，遗物用作重要代谢枢纽的质体减少。我们进一步发现 TGFBLX2定位于独特的核酸室。这个项目的目标是定义TGFBLX2如何介导寄生虫的生长。在第一个目标中，我们将确定如何 TGFBLX2调节apicoplast遗传。在第二个目标中，我们将表征 TGFBLX2所在的围核室。这些研究很重要因为它们会揭示细胞核与凋亡核之间的新型相互作用。在此外，这些发现可能与相关病原体有关，因为TGFBLX2为在疟原虫和其他Apicomplexans中保守。