Vps4属于I型AAA+ ATPase酶家族蛋白,它和内体蛋白分选转运装置III（ESCRTIII）一起在多囊体的形成、细胞质分裂和逆转录病毒如HIV的出芽等膜分裂过程中起关键作用，因此具有重要的生理功能。ESCRTIII复合体由4个蛋白组成，它们被招募到膜上后组装形成复合体帮助膜的弯曲并促进膜分裂。ESCRTIII复合体需要解开成单体以被循环使用。Vps4的作用就是利用水解ATP的能量将ESCRTIII解开。当细胞质中的Vps4二体或单体被招募到膜上与ESCRTIII结合后，会形成具有很高ATP酶活的寡聚体，将ESCRTIII解聚。然而，Vps4是如何利用水解ATP的能量将ESCRTIII复合体解开的问题一直未得到解决。本项目旨在通过研究Vps4活性寡聚体和Vps4与底物ESCRTIII形成的复合体的结构并结合生物化学和分子生物学的分析，揭示Vp4解聚ESCRTIII复合体的分子机制。

Vps4 belongs to the type-I AAA family of proteins. Vps4 functions together with ESCRTIII in membrane deformation and fission events. These cellular functions include vesicle formation at the endosome, cytokinesis and viral budding. Thus, Vps4 plays an important role in the biological processes inside cells. ESCRT-III is composed of four proteins. Once these soluble, cytoplasmic proteins are recruited to the membrane, they oligomerize into a polymer that seems to have the shape of concentric rings or spirals to facilitate the membrane deformation and fission events. Vps4 disassembles ESCRT-III polymers by using the energy from ATP hydrolysis, thereby recycling the ESCRT-III proteins for further rounds of membrane sorting. Previous studies indicate that Vps4 activity is regulated by its recruitment from the cytoplasm to ESCRT-III on the membrane, where Vps4 oligomerizes into an active ATPase. However, the mechanism underlying the disassembly of ESCRTIII by Vps4 is still unknown. In this project, we are aiming to study the structures and functions of Vps4 oligomers, and the Vps4-ESCRTIII complex by using the electron microscopy and the methods of biochemistry and molecular biology, in order to elucidate the molecular mechanism of how ESCRTIII is disassembled by Vps4.