Ubiquitin-Like Molecules and Cancer Laboratory, Proteomics Unit, CIC bioGUNE, CIBERehd, Spain.
Biochem Soc Trans. 2010 Feb;38(Pt 1):40-5. doi: 10.1042/BST0380040.
Ubiquitylation provides a rapid alternative to control the activity of crucial cellular factors through the remodelling of a target protein. Diverse ubiquitin chains are recognized by domains with affinity for UBDs (ubiquitin-binding domains) present in receptor/effector proteins. Interestingly, some proteins contain more than one UBD and the preservation of this structure in many species suggests an evolutionary advantage for this topology. Here, we review some typical proteins that naturally contain more than one UBD and emphasize how such structures contribute to the mechanism they mediate. Characteristics such as higher affinities for polyubiquitin chains and chain-linkage preferences can be replicated by the TUBEs (tandem ubiquitin-binding entities). Furthermore, TUBEs show two additional properties: protection of ubiquitylated substrates from deubiquitylating enzymes and interference with the action of the proteasome. Consequently, TUBEs behave as 'ubiquitin traps' that efficiently capture endogenous ubiquitylated proteins. Interpretations and hypothetical models proposed by different groups to understand the synchronous action of multiple UBDs are discussed herein.
泛素化通过重塑靶蛋白为关键细胞因子的活性提供了一种快速的替代方法。不同的泛素链被具有与受体/效应蛋白中存在的 UBD（泛素结合结构域）亲和力的结构域识别。有趣的是，一些蛋白质含有不止一个 UBD，并且这种结构在许多物种中的保留表明这种拓扑结构具有进化优势。在这里，我们回顾了一些天然含有多个 UBD 的典型蛋白质，并强调了这种结构如何促成它们介导的机制。更高的多泛素链亲和力和链连接偏好等特性可以通过 TUBEs（串联泛素结合实体）复制。此外，TUBEs 还具有另外两个特性：保护被泛素化的底物免受去泛素化酶的作用，以及干扰蛋白酶体的作用。因此，TUBEs 充当“泛素陷阱”，有效地捕获内源性泛素化蛋白质。本文讨论了不同小组提出的用于理解多个 UBD 同步作用的解释和假设模型。
