Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Cell. 2011 Mar 4;144(5):769-81. doi: 10.1016/j.cell.2011.01.035.
Ubiquitin chains of different topologies trigger distinct functional consequences, including protein degradation and reorganization of complexes. The assembly of most ubiquitin chains is promoted by E2s, yet how these enzymes achieve linkage specificity is poorly understood. We have discovered that the K11-specific Ube2S orients the donor ubiquitin through an essential noncovalent interaction that occurs in addition to the thioester bond at the E2 active site. The E2-donor ubiquitin complex transiently recognizes the acceptor ubiquitin, primarily through electrostatic interactions. The recognition of the acceptor ubiquitin surface around Lys11, but not around other lysines, generates a catalytically competent active site, which is composed of residues of both Ube2S and ubiquitin. Our studies suggest that monomeric E2s promote linkage-specific ubiquitin chain formation through substrate-assisted catalysis.
泛素链的不同拓扑结构会引发不同的功能后果，包括蛋白质降解和复合物的重组。大多数泛素链的组装是由 E2 促进的，但这些酶如何实现连接特异性尚不清楚。我们发现，K11 特异性的 Ube2S 通过一种必不可少的非共价相互作用来定向供体泛素，这种相互作用除了在 E2 活性位点的硫酯键之外还会发生。E2-供体泛素复合物会暂时识别受体泛素，主要是通过静电相互作用。对受体泛素表面赖氨酸 11 周围的识别，但不是其他赖氨酸周围的识别，产生了一个具有催化能力的活性位点，该活性位点由 Ube2S 和泛素的残基组成。我们的研究表明，单体 E2 通过底物辅助催化促进连接特异性泛素链的形成。
