ASPECTS OF HIV-1 BUDDING

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 而子项目的主要调查员可能是由其他来源提供的， 包括其它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。 逆转录病毒出芽与出芽进入多泡体（MVB）的囊泡的形成有许多相似之处，并且这两个过程都利用一组共同的称为ESCRT蛋白的细胞蛋白。目前的模型认为，这些复合物之一，ESCRT-III，形成一个膜相关的晶格和功能的囊泡/病毒释放的最后阶段。ESCRT-III晶格还招募了一个ATP酶，称为VPS 4，它使用ATP水解的能量从膜上释放组装的ESCRT-III蛋白。VPS 4 ATP酶活性是HIV-1出芽和MVB囊泡形成所必需的。重要的是，VPS 4活性受几种VPS 4相互作用蛋白的调节，例如VTA 1，它可以作为VPS 4p的正调节因子。Vps 4蛋白在两种寡聚状态之间循环：二聚体（不存在ATP）和十二聚体（ATP结合形式）。我们的目标是确定单独或与辅助蛋白Vta 1复合的Vps 4活性形式的晶体结构。

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.