CHARACTERIZATION OF THE NUCLEAR PORECOMPLEX OF THE AFRICAN TRYPANOSOME

非洲锥虫核孔复合物的特征

• 批准号: 8361503
• 负责人: Brian T Chait
• 金额: $ 2.61万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361503
• 关键词: Affinity; African; Architecture; Bioinformatics; Cell Nucleus; Coated vesicle; Complex; Cytoplasm; Eukaryota; Evolution; Funding; Genomics; Grant; Left; Manuscripts; Mediating; Molecular; National Center for Research Resources; Nuclear; Nuclear Pore Complex; Principal Investigator; Procedures; Proteomics; Publishing; Research; Research Infrastructure; Resolution; Resources; Source; Trypanosoma; Trypanosoma brucei brucei; United States National Institutes of Health; Work; cost; improved; macromolecular assembly; macromolecule; scaffold

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The nuclear pore complex (NPC) is a massive macromolecular assembly, unique to Eukaryotes, that mediates bidirectional exchange of material between the nucleus and cytoplasm. Until recently, the evolutionary origin of the NPC was unknown, leaving a major gap in our understanding of the origin of the Eukaryota. Prior bioinformatic studies led to the conclusion that the Last Common Eukaryotic Ancestor (LCEA) possessed a rather primitive ancestral NPC, passing few components to its highly divergent modern descendants. Using a proteomic/genomic approach, we show that the LCEA actually possessed an NPC with a surprisingly modern architecture. Moreover, we have established that all NPCs have a fundamentally similar scaffold architecture that resembles the architecture of coated vesicles. Our findings strongly support the hypothesis that NPCs share a common ancestry with vesicle coating complexes, and that both were established very early in eukaryotic evolution. A manuscript describing this work has been published (23. J.A. DeGrasse, K.N. DuBois, D. Devos, T.N. Siegel, A. Sali, M.C. Field, M.P. Rout, B.T. Chait "Evidence for a shared nuclear pore complex architecture that is conserved from the last common eukaryotic ancestor" Molecular & Cellular Proteomics, 8 (2009) 2119-30). We are now continuing to improve our affinity isolation procedures for gaining higher resolution information about the architecture, function an evolution of the T. brucei NPC and are obtaining very promising results.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 核孔复合物（NPC）是真核生物特有的一种大分子组装体，介导细胞核和细胞质之间的双向物质交换。直到最近，NPC的进化起源还不清楚，这给我们对真核生物起源的理解留下了重大空白。先前的生物信息学研究得出的结论是，最后共同真核祖先（LCEA）拥有一个相当原始的祖先NPC，将很少的组件传递给其高度分化的现代后代。使用蛋白质组学/基因组学方法，我们表明，LCEA实际上拥有一个NPC与一个令人惊讶的现代建筑。此外，我们已经确定，所有的NPC具有基本相似的支架结构，类似于包被囊泡的结构。我们的研究结果有力地支持了这一假设，即NPC与囊泡涂层复合物有着共同的祖先，并且两者都是在真核生物进化的早期建立的。描述这项工作的手稿已出版（23。 J.A. DeGrasse，K.N.杜波依斯，D. Devos，T.N.西格尔，A. M.C.萨利Field，M.P. Rout，B.T. Chait“Evidence for a shared nuclear pore complex architecture that is conserved from the last common eukaryotic ancestor”Molecular & Cellular Proteomics，8（2009）2119-30）。 我们现在正在继续改进我们的亲和分离程序，以获得关于T.布氏鼻咽癌，并取得了非常有希望的结果。