Structural insights for HIV-1 therapeutic strategies targeting Vif.
Structural insights for HIV-1 therapeutic strategies targeting Vif.
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针对VIF的HIV-1治疗策略的结构见解。
DOI：
10.1016/j.tibs.2014.07.001
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发表时间：
2014-09
影响因子：
13.8
通讯作者：
Smith HC
中科院分区：
文献类型：
--
作者：
Salter JD;Morales GA;Smith HC
HIV-1病毒感染因子（Vif）是HIV-1感染所必需的一种病毒辅助蛋白，其主要作用是将载脂蛋白B编辑催化亚基样3 （APO-BEC3）家族的抗逆转录病毒因子募集到E3泛素连接酶复合体中，以进行多泛素化和蛋白酶体降解。近全长Vif蛋白与长链蛋白（Elo）B/C、核心结合因子(CBF)β和Cullin (Cul)5复合物的晶体结构表明Vif具有一种新的结构褶皱。在我们看来，结构数据不仅揭示了决定Vif稳定性和与细胞蛋白相互作用的蛋白-蛋白相互作用位点，而且还揭示了驱动Vif二聚体的基序，这在Vif功能和HIV-1感染中是必不可少的。vif介导的蛋白质-蛋白质相互作用是一种新型抗逆转录病毒疗法对抗艾滋病的极好靶点。
HIV-1 viral infectivity factor (Vif) is a viral accessory protein that is required for HIV-1 infection due largely to its role in recruiting antiretroviral factors of the APO-BEC3 (apolipoprotein B editing catalytic subunit-like 3) family to an E3 ubiquitin ligase complex for polyubiquitylation and proteasomal degradation. The crystal structure of the (near) full-length Vif protein in complex with Elongin (Elo)B/C, core-binding factor (CBF)β and Cullin (Cul)5 revealed that Vif has a novel structural fold. In our opinion the structural data revealed not only the protein–protein interaction sites that determine Vif stability and interaction with cellular proteins, but also motifs driving Vif homodimerization, which are essential in Vif functionality and HIV-1 infection. Vif-mediated protein–protein interactions are excellent targets for a new class of antiretroviral therapeutics to combat AIDS.