Tsg101, an inactive homologue of ubiquitin ligase E2, interacts specifically with human immunodeficiency virus type 2 Gag polyprotein and results in increased levels of ubiquitinated Gag
Tsg101, an inactive homologue of ubiquitin ligase E2, interacts specifically with human immunodeficiency virus type 2 Gag polyprotein and results in increased levels of ubiquitinated Gag
复制标题
DOI：
10.1128/jvi.76.22.11226-11235.2002
复制
发表时间：
2002-11-01
影响因子：
5.4
通讯作者：
Allen, JF
中科院分区：
文献类型：
--
作者：
Myers, EL;Allen, JF
逆转录病毒颗粒萌发和释放的最后阶段需要GAG的晚期结构域(L)。最近，泛素和泛素连接酶被认为与逆转录病毒萌发的晚期有关。在酵母双杂交筛选T细胞cDNA文库以鉴定与人类免疫缺陷病毒2型(HIV-2)Gag多聚蛋白相互作用的细胞蛋白时，我们鉴定了泛素连接酶E2的非活性同源物Tsg101。Tsg101和HIV-2 Gag在体外和体内都有特异性的相互作用。这种相互作用需要HIV-2Gag的p6结构域中的L结构域PTAPP基序和Tsg101的N端UBC-连接同源结构域。Tsg101被整合到HIV-2病毒粒子中。Tsg101的N端UBC结合同源结构域的表达抑制HIV-2病毒颗粒的释放。Tsg101的过表达导致HIV-2 Gag泛素化水平的增加。我们的结果为在病毒生命周期的后期阶段，由病毒Gag蛋白介导的细胞泛素化机制的招募提供了证据。
The final stages of budding and release of a retroviral particle from the cell require the late (L) domain of Gag. Recently, ubiquitin and ubiquitin ligases have been implicated in the late stages of retroviral budding. In a yeast two-hybrid screen of a T-cell cDNA library to identify cellular proteins that interact with human immunodeficiency virus type 2 (HIV-2) Gag polyprotein, we identified Tsg101, an inactive homologue of ubiquitin ligase E2. Tsg101 and HIV-2 Gag interact specifically in vitro and in vivo. The interaction requires the L domain PTAPP motif in the p6 domain of HIV-2 Gag and the N-terminal Ubc-conjugation homology domain of Tsg101. Tsg101 is incorporated into HIV-2 virions. Expression of the N-terminal Ubc-conjugation homology domain of Tsg101 inhibits the release of HIV-2 virus particles. Overexpression of Tsg101 results in an increase in the level of ubiquitination of HIV-2 Gag. Our results provide evidence for recruitment of the ubiquitination machinery of the cell during late stages of the viral life cycle, mediated by the viral Gag protein.