STRUCT ANALYSIS OF THE PROTEIN NETWORK OF SORTING AT MULTIVESICULAR BODIES:HIV

多维体分选蛋白网络的结构分析：HIV

• 批准号: 7721876
• 负责人: JAMES Bryant HURLEY
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721876
• 关键词: Binding; Biochemical; C-terminal; Complex; Computer Retrieval of Information on Scientific Projects Database; Enzymes; Funding; Goals; Grant; HIV; HIV-1; Human; Institution; Lysosomes; Membrane; Multiprotein Complexes; Multivesicular Body; N-terminal; Protein Analysis; Proteins; Research; Research Personnel; Resources; Sorting - Cell Movement; Source; Structure; Tertiary Protein Structure; Testing; United States National Institutes of Health; Vacuole; Viral; Yeasts; human AIP1 protein; particle; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HIV-1 particle assembly and release depend on the human proteins AIP1/Alix and Vps4A/B, and four human protein complexes: Hrs/STAM and ESCRT-I, II, and III. These proteins and complexes are conserved from yeast to human, and their normal function is to sort monoubiquitinated receptors, enzymes, and other cargo to the lysosome or vacuole. Inactivation of any one of several proteins tested in this network blocks HIV release and infectivity. We have begun to systematically determine the structures of domains, proteins, and multiprotein complexes in this network, and we have already solved the structures of the Vps27 (yeast Hrs) FYVE domain, the N-terminal half of Bro1 (yeast AIP1/Alix), and the nearly intact yeast ESCRT-II complex (Vps22,Vps25, and Vps36). Over the next two years we plan to 1) solve the structure of the ESCRT-I (Vps23, Vps28, Vps37) complex from yeast or human; 2) carry out a structural and functional analysis of ESCRT-II taking our 3.6 ¿ complex structure as a starting point; 3) solve the structure of the C-terminal half of Bro1 or AIP1/Alix; and 4) characterize the membrane and viral late domain binding of AIP1/Alix. In the long term our goal is the complete structural and biochemical characterization of the entire network.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 HIV-1 颗粒的组装和释放取决于人类蛋白 AIP1/Alix 和 Vps4A/B，以及四种人类蛋白复合物：Hrs/STAM 和 ESCRT-I、II 和 III。这些蛋白质和复合物从酵母到人类都是保守的，它们的正常功能是将单泛素化受体、酶和其他货物分选到溶酶体或液泡。该网络中测试的几种蛋白质中任何一种的失活都会阻止艾滋病毒的释放和传染性。我们已经开始系统地确定该网络中的结构域、蛋白质和多蛋白复合物的结构，并且我们已经解决了Vps27（酵母Hrs）FYVE结构域、Bro1（酵母AIP1/Alix）的N端一半和几乎完整的酵母ESCRT-II复合物（Vps22、Vps25和Vps36）的结构。在接下来的两年里，我们计划 1) 解析来自酵母或人类的 ESCRT-I (Vps23、Vps28、Vps37) 复合物的结构； 2）以我们的3.6¿复杂结构为起点，对ESCRT-II进行结构和功能分析； 3) 解析Bro1或AIP1/Alix的C端一半的结构； 4) 表征 AIP1/Alix 的膜和病毒晚期结构域结合。从长远来看，我们的目标是完整地表征整个网络的结构和生化特征。