Core-Binding Factor 尾 Increases the Affinity between Human Cullin 5 and HIV-1 Vif within an E3 Ligase Complex

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• 作者：Jason D. Salter ; Geoffrey M. Lippa ; Ivan A. Belashov ; Joseph E. Wedekind
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：November 6, 2012
• 年：2012
• 卷：51
• 期：44
• 页码：8702-8704
• 全文大小：198K
• 年卷期：v.51,no.44(November 6, 2012)
• ISSN：1520-4995

文摘

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 尾 (CBF尾) in contrast to cellular substrate receptors. We observed calorimetrically that Cul5 binds tighter to full-length Vif^(1鈥?92)/EloB/C/CBF尾 (K_d = 5 卤 2 nM) than to Vif^(95鈥?92)/EloB/C (K_d = 327 卤 40 nM), which cannot bind CBF尾. A comparison of heat capacity changes supports a model in which CBF尾 prestabilizes Vif^(1鈥?92) relative to Vif^(95鈥?92), consistent with a stronger interaction of Cul5 with Vif鈥檚 C-terminal Zn²⁺-binding motif. An additional interface between Cul5 and an N-terminal region of Vif appears to be plausible, which has therapeutic design implications.