title: Core-binding factor β increases the affinity between human Cullin 5 and HIV-1 Vif within an E3 ligase complex.
abstract: HIV-1 Vif masquerades as a receptor for a cellular E3 ligase harboring Elongin B, Elongin C, and Cullin 5 (EloB/C/Cul5) proteins that facilitate degradation of the antiretroviral factor APOBEC3G (A3G). This Vif-mediated activity requires human core-binding factor β (CBFβ) in contrast to cellular substrate receptors. We observed calorimetrically that Cul5 binds tighter to full-length Vif((1-192))/EloB/C/CBFβ (K(d) = 5 ± 2 nM) than to Vif((95-192))/EloB/C (K(d) = 327 ± 40 nM), which cannot bind CBFβ. A comparison of heat capacity changes supports a model in which CBFβ prestabilizes Vif((1-192)) relative to Vif((95-192)), consistent with a stronger interaction of Cul5 with Vif's C-terminal Zn(2+)-binding motif. An additional interface between Cul5 and an N-terminal region of Vif appears to be plausible, which has therapeutic design implications.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, United States.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Salter
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Lippa
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Belashov
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Wedekind
mesh_terms: D050658:Core Binding Factor beta Subunit / Q000502:physiology*; D044842:Cullin Proteins / Q000378:metabolism*; D006801:Humans; D013816:Thermodynamics; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C493692:CBFB protein, human; C496871:CUL5 protein, human; D050658:Core Binding Factor beta Subunit; D044842:Cullin Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D044767:Ubiquitin-Protein Ligases