ASPECTS OF HIV-1 BUDDING

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。 逆转录病毒的萌发与萌发成多泡小体的囊泡的形成有许多相似之处，这两个过程都利用了一组共同的细胞蛋白，称为ESCRT蛋白。目前的模型认为，这些复合体之一，ESCRT-III，形成了一个膜相关的晶格，并在囊泡/病毒释放的最后阶段发挥作用。ESCRT-III晶格还招募了一种名为Vps4的ATPase，它利用ATP水解的能量将组装好的ESCRT-III蛋白从膜上释放出来。Vps4 ATPase活性是HIV-1萌发和MVB囊泡形成所必需的。重要的是，Vps4的活性受几种与Vps4相互作用的蛋白质的调节，例如VTA1，它可以作为VPS4p的正向调节因子。Vps4蛋白在两种寡聚状态之间循环：二聚体(在没有ATP的情况下)和十二聚体(以ATP结合的形式)。我们的目标是确定Vps4活性形式单独或在与辅助蛋白Vta1的复合体中的晶体结构。

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. Retrovirus budding shares a number of similarities with the formation of vesicles that bud into the multivesicular body (MVB), and both processes utilize a common set of cellular proteins called ESCRT proteins. Current models hold that one of these complexes, ESCRT-III, forms a membrane-associated lattice and functions in the final stages of vesicle/viron release. The ESCRT-III lattice also recruits an ATPase, called VPS4, which uses the energy of ATP hydrolysis to release the assembled ESCRT-III proteins from the membrane. VPS4 ATPase activity is required for HIV-1 budding and the formation of MVB vesicles. Importantly, VPS4 activity is regulated by several VPS4-interacting proteins, for example, VTA1, which can act as a positive regulator of VPS4p. Vps4 protein cycles between two oligomeric states: dimeric (in absence of ATP) and dodecameric ( in ATP-bound form). Our goal is to determine the crystallographic structure of the Vps4 active form alone or in the complex with the accessory protein Vta1.