E2s: structurally economical and functionally replete.
E2s: structurally economical and functionally replete.
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E2S：结构上经济和功能上充满。
DOI：
10.1042/bj20100985
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Klevit RE
中科院分区：
文献类型：
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作者：
Wenzel DM;Stoll KE;Klevit RE
泛素化是一种涉及无数细胞调控和疾病途径的翻译后修饰途径。泛素（Ub）转移级联需要三种酶的活性：Ub激活酶（E1）、Ub偶联酶（E2）和Ub连接酶（E3）。因为E2负责E3选择和底物修饰，E2在Ub传递途径的核心起作用，并负责Ub细胞信号的多样性。目前有超过90种E2s的三维结构，包括单独的和与蛋白质结合伙伴的复合结构，提供了关于E2s如何被各种蛋白质识别的丰富信息。在这篇综述中，我们描述了典型的E2/E3接口，并讨论了当前识别同源E2/E3伙伴的方法的局限性。我们提出了非规范的e2 -蛋白质相互作用，并强调了e2的经济性，因为它们能够在其相对小而紧凑的催化结构域的几乎每个表面上促进许多蛋白质相互作用。最后，我们比较了共轭E2~Ub物种的结构，它们独特的蛋白质相互作用，以及准备转移Ub的物种提供的机制见解。
Ubiquitination is a post-translational modification pathway involved in myriad cellular regulation and disease pathways. The ubiquitin (Ub) transfer cascade requires three enzyme activities: a Ub-activating (E1) enzyme, a Ub-conjugating (E2) enzyme, and a Ub ligase (E3). Because the E2 is responsible both for E3 selection and substrate modification, E2s function at the heart of the Ub transfer pathway and are responsible for much of the diversity of Ub cellular signaling. There are currently over ninety three-dimensional structures of E2s, both alone and in complex with protein binding partners, providing a wealth of information regarding how E2s are recognized by a wide variety of proteins. In this review, we describe the prototypical E2/E3 interface and discuss limitations of current methods to identify cognate E2/E3 partners. We present non-canonical E2-protein interactions and highlight the economy of E2s in their ability to facilitate many protein-protein interactions at nearly every surface on their relatively small, compact catalytic domain. Lastly, we compare the structures of conjugated E2~Ub species, their unique protein interactions, and the mechanistic insights provided by species that are poised to transfer Ub.