Different roles for two ubiquitin-like domains of ISG15 in protein modification
Different roles for two ubiquitin-like domains of ISG15 in protein modification
复制标题
ISG15 的两个泛素样结构域在蛋白质修饰中的不同作用
DOI：
10.1074/jbc.m800162200
复制
发表时间：
2008-05-09
影响因子：
4.8
通讯作者：
Hu, Hong-Yu
中科院分区：
文献类型：
--
作者：
Chang, Yong-Gang;Yan, Xian-Zhong;Hu, Hong-Yu
干扰素刺激基因15（interferon-stimulated gene 15，ISG 15）是一种新型的泛素样蛋白（ubiquitin-like，UbL）修饰物，其结构中含有两个UbL结构域。我们研究了两个UbL结构域在ISG 15蛋白修饰（ISGylation）中的不同作用以及流感B病毒NS 1蛋白（NS 1 B）对该途径调控的影响。结果表明，尽管C-末端结构域足以将ISG 15连接到UBE 1 L和UbcH 8，但N-末端结构域在活化和转巯基化步骤中是不稳定的，但对于E3介导的ISG 15从UbcH 8有效转移到其底物是必需的。NS 1B特异性结合ISG 15的N-末端结构域，但不影响ISG 15通过硫酯键与其活化和缀合酶的连接。然而，在干扰素治疗后，它确实抑制细胞ISG 15缀合物的形成。我们认为ISG 15的N-末端UbL结构域主要在连接步骤中起作用，NS 1B通过与E3连接酶竞争结合到N-末端结构域来抑制ISG化。
ISG15 (interferon-stimulated gene 15) is a novel ubiquitin-like (UbL) modifier with two UbL domains in its architecture. We investigated different roles for the two UbL domains in protein modification by ISG15 (ISGylation) and the impact of Influenza B virus NS1 protein (NS1B) on regulation of the pathway. The results show that, although the C-terminal domain is sufficient to link ISG15 to UBE1L and UbcH8, the N-terminal domain is dispensable in the activation and transthiolation steps but required for efficient E3-mediated transfer of ISG15 from UbcH8 to its substrates. NS1B specifically binds to the N-terminal domain of ISG15 but does not affect ISG15 linkage via a thioester bond to its activating and conjugating enzymes. However, it does inhibit the formation of cellular ISG15 conjugates upon interferon treatment. We propose that the N-terminal UbL domain of ISG15 mainly functions in the ligation step and NS1B inhibits ISGylation by competing with E3 ligases for binding to the N-terminal domain.