Balakirev Maxim Y, Jaquinod Michel, Haas Arthur L, Chroboczek Jadwiga
Institut de Biologie Structurale, Grenoble 38027. Département de Biologie Moléculaire et Structurale, CEA, Grenoble 38054, France.
J Virol. 2002 Jun;76(12):6323-31. doi: 10.1128/jvi.76.12.6323-6331.2002.
The invasion strategy of many viruses involves the synthesis of viral gene products that mimic the functions of the cellular proteins and thus interfere with the key cellular processes. Here we show that adenovirus infection is accompanied by an increased ubiquitin-cleaving (deubiquitinating) activity in the host cells. Affinity chromatography on ubiquitin aldehyde (Ubal), which was designed to identify the deubiquitinating proteases, revealed the presence of adenovirus L3 23K proteinase (Avp) in the eluate from adenovirus-infected cells. This proteinase is known to be necessary for the processing of viral precursor proteins during virion maturation. We show here that in vivo Avp deubiquitinates a number of cellular proteins. Analysis of the substrate specificity of Avp in vitro demonstrated that the protein deubiquitination by this enzyme could be as efficient as proteolytic processing of viral proteins. The structural model of the Ubal-Avp interaction revealed some similarity between S1-S4 substrate binding sites of Avp and ubiquitin hydrolases. These results may reflect the acquisition of an advantageous property by adenovirus and may indicate the importance of ubiquitin pathways in viral infection.
许多病毒的入侵策略涉及合成模仿细胞蛋白功能的病毒基因产物，从而干扰关键的细胞过程。在此我们表明，腺病毒感染伴随着宿主细胞中泛素裂解（去泛素化）活性的增加。在泛素醛（Ubal）上进行亲和层析，旨在鉴定去泛素化蛋白酶，结果显示在腺病毒感染细胞的洗脱液中存在腺病毒L3 23K蛋白酶（Avp）。已知这种蛋白酶在病毒粒子成熟过程中对病毒前体蛋白的加工是必需的。我们在此表明，在体内Avp可使多种细胞蛋白去泛素化。对Avp体外底物特异性的分析表明，该酶介导的蛋白去泛素化作用与病毒蛋白的蛋白水解加工一样有效。Ubal-Avp相互作用的结构模型揭示，Avp的S1-S4底物结合位点与泛素水解酶之间存在一些相似性。这些结果可能反映了腺病毒获得了一种有利特性，也可能表明泛素途径在病毒感染中的重要性。
