Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release
Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release
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DOI：
10.1073/pnas.0909176106
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发表时间：
2009-12-15
影响因子：
11.1
通讯作者：
Saiardi, Adolfo
中科院分区：
文献类型：
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作者：
Azevedo, Cristina;Burton, Adam;Saiardi, Adolfo
高能肌醇焦磷酸，如IP7（二磷酸肌醇五磷酸），可以直接将β-磷酸提供给预磷酸化的丝氨酸残基，产生焦磷酸化的蛋白质。在这里，我们表明，AP-3的β亚基，网格蛋白相关的蛋白复合物所需的HIV-1的释放，是IP7介导的焦磷酸化的目标。我们已经确定了Kif 3A，驱动蛋白超家族的马达蛋白，作为AP 3B 1结合的合作伙伴，并证明Kif 3A，像AP-3复合物，参与了HIV-1 Gag释放所需的细胞内过程。重要的是，IP7介导的AP 3B 1焦磷酸化调节与Kif 3A的相互作用，因此影响HIV-1病毒样颗粒的释放。这项研究确定了一个由IP7介导的焦磷酸化调控的细胞过程。
High-energy inositol pyrophosphates, such as IP7 (diphosphoinositol pentakisphosphate), can directly donate beta-phosphate to a prephosphorylated serine residue generating pyrophosphorylated proteins. Here, we show that the beta subunit of AP-3, a clathrin-associated protein complex required for HIV-1 release, is a target of IP7-mediated pyrophosphorylation. We have identified Kif3A, a motor protein of the kinesin superfamily, as an AP3B1-binding partner and demonstrate that Kif3A, like the AP-3 complex, is involved in an intracellular process required for HIV-1 Gag release. Importantly, IP7-mediated pyrophosphorylation of AP3B1 modulates the interaction with Kif3A and, as a consequence, affects the release of HIV-1 virus-like particles. This study identifies a cellular process that is regulated by IP7-mediated pyrophosphorylation.