Structural Insights into Non-canonical Ubiquitination Catalyzed by SidE
Structural Insights into Non-canonical Ubiquitination Catalyzed by SidE
复制标题
SidE 催化的非典型泛素化的结构见解
DOI：
10.1016/j.cell.2018.04.023
复制
发表时间：
2018-05-17
期刊：
影响因子：
64.5
通讯作者：
Gao, Pu
中科院分区：
文献类型：
--
作者：
Wang, Yong;Shi, Miao;Gao, Pu
泛素化是真核生物中最重要的信号转导机制之一。传统的泛素化由普遍保守的E1-E2-E3三酶级联反应以ATP依赖的方式催化。新鉴定的病原体嗜肺军团菌的SidE家族效应子通过不同的机制泛素化几种人类蛋白质，而不参与任何常规的泛素化机制。我们现在报告的晶体结构的SidE单独和复杂的泛素，NAD，ADP-核糖，从而捕获不同的构象的SidE之前和之后的泛素和配体结合。结合到mART和PDE结构域的泛素结构揭示了SidE催化的两个反应步骤的几个独特特征。此外，结构和生化结果表明，SidE家族成员不识别底物蛋白的特定结构折叠。我们的研究为功能观察提供了结构解释，并对这种非经典泛素化机制提供了新的见解。
Ubiquitination constitutes one of the most important signaling mechanisms in eukaryotes. Conventional ubiquitination is catalyzed by the universally conserved E1-E2-E3 three-enzyme cascade in an ATP-dependent manner. The newly identified SidE family effectors of the pathogen Legionella pneumophila ubiquitinate several human proteins by a different mechanism without engaging any of the conventional ubiquitination machinery. We now report the crystal structures of SidE alone and in complex with ubiquitin, NAD, and ADP-ribose, thereby capturing different conformations of SidE before and after ubiquitin and ligand binding. The structures of ubiquitin bound to both mART and PDE domains reveal several unique features of the two reaction steps catalyzed by SidE. Further, the structural and biochemical results demonstrate that SidE family members do not recognize specific structural folds of the substrate proteins. Our studies provide both structural explanations for the functional observations and new insights into the molecular mechanisms of this non-canonical ubiquitination machinery.