Structural Studies of Alix and ESCRT Complexes in HIV-1 Budding

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Structural Studies of Alix and ESCRT Complexes in HIV-1 Budding HIV-1 particle assembly and release depend on a protein network that includes Alix and Vps4A/B, and four multiprotein 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. In past effort in this project, we mapped the molecular interactions between HIV and ESCRT components at the level of individual protein domains and characterized the binding affinities and relevant structures of the components involved in these interactions. Looking ahead, the goals of this project will be to reconstitute the assembly and ESCRT-mediated budding of HIV-1 in vitro, and, in collaboration with Eric Freed, NCI, to design means for inhibiting HIV-1 budding from cells.