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.

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Carlson, Lars-Anders; Hurley, James H (2012) In vitro reconstitution of the ordered assembly of the endosomal sorting complex required for transport at membrane-bound HIV-1 Gag clusters. Proc Natl Acad Sci U S A 109:16928-33
Hurley, James H; Odorizzi, Greg (2012) Get on the exosome bus with ALIX. Nat Cell Biol 14:654-5
Ren, Xuefeng; Hurley, James H (2011) Proline-rich regions and motifs in trafficking: from ESCRT interaction to viral exploitation. Traffic 12:1282-90
Kim, Sung-Eun; Liu, Fa; Im, Young Jun et al. (2011) Elucidation of New Binding Interactions with the Tumor Susceptibility Gene 101 (Tsg101) Protein Using Modified HIV-1 Gag-p6 Derived Peptide Ligands. ACS Med Chem Lett 2:337-341
Ren, Xuefeng; Hurley, James H (2011) Structural basis for endosomal recruitment of ESCRT-I by ESCRT-0 in yeast. EMBO J 30:2130-9
Wollert, Thomas; Hurley, James H (2010) Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature 464:864-9
Im, Young Jun; Kuo, Lillian; Ren, Xuefeng et al. (2010) Crystallographic and functional analysis of the ESCRT-I /HIV-1 Gag PTAP interaction. Structure 18:1536-47
Wollert, Thomas; Wunder, Christian; Lippincott-Schwartz, Jennifer et al. (2009) Membrane scission by the ESCRT-III complex. Nature 458:172-7