The linkage specificity determination of Ube2g2-gp78 mediated polyubiquitination
The linkage specificity determination of Ube2g2-gp78 mediated polyubiquitination
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Ube2g2-gp78介导的多聚泛素化的连锁特异性测定
DOI：
10.1016/j.bbrc.2016.04.029
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发表时间：
2016-05-13
影响因子：
3.1
通讯作者：
Li, Wei
中科院分区：
文献类型：
--
作者：
Gao, Fengyi;Shang, Yongliang;Li, Wei
多聚泛素链的连接特异性或拓扑结构对于其在多种细胞过程中的作用至关重要。以往的研究更多关注首个泛素部分的连接特异性，然而，对于较长多聚泛素链中连接特异性的编辑机制却知之甚少。gp78及其相关的E2酶Ube2g2催化赖氨酸48（K48）连接的多聚泛素链，以促进靶蛋白的降解。在此，我们表明整个多聚泛素链的连接特异性是由首个泛素分子的结合方式决定的，而非后续的泛素分子。进一步研究发现，在K48连接的多聚泛素链增长过程中，gp78的CUE结构域起着校对机制的作用，以确保连接特异性。总之，我们的研究揭示了较长多聚泛素链连接特异性确定背后的一种新机制。（C）2016爱思唯尔公司。保留所有权利。
Polyubiquitin chain linkage specificity or topology is essential for its role in diverse cellular processes. Previous studies pay more attentions to the linkage specificity of the first ubiquitin moieties, whereas, little is known about the editing mechanism of linkage specificity in longer polyubiquitin chains. gp78 and its cognate E2-Ube2g2 catalyze lysine48 (K48)-linked polyubiquitin chains to promote the degradation of targeted proteins. Here, we show that the linkage specificity of the entire polyubiquitin chain is determined by the conjugation manner of the first ubiquitin molecule but not the following ones. Further study discovered that the gp78 CUE domain works as a proofreading machine during the growth of K48-linked polyubiquitin chains to ensure the linkage specificity. Together, our studies uncover a novel mechanism underlying the linkage specificity determination of longer polyubiquitin chains. (C) 2016 Elsevier Inc. All rights reserved.