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.
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