Middleton Adam J, Wright Joshua D, Day Catherine L
Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
J Mol Biol. 2017 Nov 10;429(22):3430-3440. doi: 10.1016/j.jmb.2017.06.008. Epub 2017 Jun 15.
Attachment of ubiquitin to proteins relies on a sophisticated enzyme cascade that is tightly regulated. The machinery of ubiquitylation responds to a range of signals, which remarkably includes ubiquitin itself. Thus, ubiquitin is not only the central player in the ubiquitylation cascade but also a key regulator. The ubiquitin E3 ligases provide specificity to the cascade and often bind the substrate, while the ubiquitin-conjugating enzymes (E2s) have a pivotal role in determining chain linkage and length. Interaction of ubiquitin with the E2 is important for activity, but the weak nature of these contacts has made them hard to identify and study. By reviewing available crystal structures, we identify putative ubiquitin binding sites on E2s, which may enhance E2 processivity and the assembly of chains of a defined linkage. The implications of these new sites are discussed in the context of known E2-ubiquitin interactions.
泛素与蛋白质的附着依赖于一个受到严格调控的复杂酶级联反应。泛素化机制对一系列信号作出反应，其中显著的包括泛素自身。因此，泛素不仅是泛素化级联反应的核心参与者，也是一个关键调节因子。泛素E3连接酶赋予级联反应特异性，并且常常结合底物，而泛素结合酶（E2s）在决定链的连接方式和长度方面具有关键作用。泛素与E2的相互作用对活性很重要，但这些相互作用的微弱性质使得它们难以被识别和研究。通过回顾现有的晶体结构，我们确定了E2s上可能的泛素结合位点，这些位点可能增强E2的持续合成能力以及特定连接方式的链的组装。在已知的E2 - 泛素相互作用的背景下讨论了这些新位点的意义。
