Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif
Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif
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DOI：
10.1038/nsmb.1497
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发表时间：
2008-11-01
影响因子：
16.8
通讯作者：
Uchiyama, Takashi
中科院分区：
文献类型：
--
作者：
Shirakawa, Kotaro;Takaori-Kondo, Akifumi;Uchiyama, Takashi
载脂蛋白B基因编码酶催化多肽样3G(APOBEC3G，简称A3G)是一种针对人类免疫缺陷病毒1型(HIV-1)的有效抗逆转录病毒宿主因子。HIV-1病毒感染性因子(VIF)通过泛素-蛋白酶体途径促进A3G的降解，从而中和A3G。最近的研究表明，蛋白激酶A(PKA)可磷酸化APOBEC3家族的另一个成员--活化诱导脱氨酶(AID)。A3G有两个可能的PKA磷酸化残基。在此，我们发现在体外和体内，PKA在Thr32处结合A3G并特异性地将其磷酸化。这种磷酸化事件减少了A3G与Vif的结合以及随后的泛素化和降解，从而促进了A3G的抗病毒活性。计算机辅助结构建模和突变研究表明，A3G Thr32和Arg24之间的相互作用对于与Vif的相互作用至关重要。这些数据表明，PKA介导的A3G的磷酸化可以调节A3G与Vif之间的相互作用。
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, referred to here as A3G) is a potent antiretroviral host factor against human immunodeficiency virus type 1 (HIV-1). HIV-1 viral infectivity factor (Vif) counteracts A3G by promoting its degradation via the ubiquitin-proteasome pathway. Recent studies demonstrated that protein kinase A (PKA) phosphorylates activation-induced deaminase (AID), another member of the APOBEC3 family. A3G has two putative PKA phosphorylation residues. Here we show that PKA binds and specifically phosphorylates A3G at Thr32 in vitro and in vivo. This phosphorylation event reduces the binding of A3G to Vif and its subsequent ubiquitination and degradation, and thus promotes A3G antiviral activity. Computer- assisted structural modeling and mutagenesis studies suggest that the interaction between A3G Thr32 and Arg24 is crucial for interaction with Vif. These data imply that PKA-mediated phosphorylation of A3G can regulate the interaction between A3G and Vif.