UBIQUITIN C-TERMINAL HYDROLASE L3 COMPLEX WITH UBIQUITIN-BASED SUICIDE SUBSTRATE

泛素 C 末端水解酶 L3 复合物与基于泛素的自杀底物

• 批准号: 8361612
• 负责人: Hidde L. Ploegh
• 金额: $ 0.33万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361612
• 关键词: Antigen Presentation; Architecture; Bacteria; Complex; Data; Funding; Grant; Host Defense Mechanism; Malaria; Membrane Protein Traffic; Molecular; National Center for Research Resources; Orthologous Gene; Parasites; Pathway interactions; Plasmodium falciparum; Principal Investigator; Proteins; Regulation; Research; Research Infrastructure; Resources; Source; Specificity; System; Ubiquitin; United States National Institutes of Health; Virus; base; cost; interest; multicatalytic endopeptidase complex; novel strategies; pathogen; structural biology; suicide substrates; ubiquitin C-terminal hydrolase

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. A new approach to controlling malaria-causing Plasmodium falciparum aims at the parasite's ubiquitin-proteasome pathway which is essential for its survival. Since the host's defense mechanisms against pathogens rely on the ubiquitin-proteasome system in antigen presentation and in the regulation of membrane trafficking, many viruses and bacteria encode proteins that act on the ubiquitin-proteasome pathway, yet there is a near-complete lack of data on this pathway in parasites. It was shown that the mammalian UchL3 ortholog in Plasmodium falciparum (PfUchL3) possesses deubiquitinating as well as deNeddylating activity. We are interested in determining the molecular architecture of PfUchL3 and revealing the mechanisms for the dual specificity towards ubiquitin and NEDD8. To this end we prepared crystals of the complex between PfUchL3 and the ubiquitin based suicide substrate UbVME.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 一种控制导致疟疾的恶性疟原虫的新方法瞄准了这种寄生虫的泛素-蛋白酶体途径，这是其生存所必需的。由于宿主对病原体的防御机制依赖于泛素-蛋白酶体系统在抗原提呈和膜转运调节中的作用，许多病毒和细菌编码作用于泛素-蛋白酶体途径的蛋白质，然而在寄生虫中几乎完全缺乏关于这一途径的数据。 结果表明，恶性疟原虫(PfUchL3)中的哺乳动物UchL3同源基因(PfUchL3)具有去泛素化和去核苷化活性。我们感兴趣的是确定PfUchL3的分子结构，并揭示泛素和NEDD8双重特异性的机制。为此，我们制备了PfUchL3与基于泛素的自杀底物UbVME之间的络合物的晶体。