Insights into catalysis and regulation of non-canonical ubiquitination and deubiquitination by bacterial deamidase effectors
Insights into catalysis and regulation of non-canonical ubiquitination and deubiquitination by bacterial deamidase effectors
复制标题
深入了解细菌脱酰胺酶效应子对非经典泛素化和去泛素化的催化和调节
DOI：
10.1038/s41467-020-16587-w
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发表时间：
2020-06-02
影响因子：
16.6
通讯作者：
Gao, Pu
中科院分区：
文献类型：
--
作者：
Wang, Yong;Zhan, Qi;Gao, Pu
细菌效应子MavC催化宿主E2酶UBE 2N的非经典泛素化，而不参与任何常规的泛素化机制，从而消除UBE 2N在形成K63连接的泛素（Ub）链和抑制NF-κ B信号传导中的功能。我们现在报告的结构MavC的复合物与共轭UBE 2N-Ub和抑制剂蛋白Lpg 2149，以及其直系同源物，MvcA，结合到Lpg 2149的结构。UBE 2N和Ub的识别依赖于MavC的几个独特特征，这解释了MvcA不能催化泛素化。出乎意料的是，MavC和MvcA也具有针对MavC介导的泛素化的去泛素化酶活性，突出了MavC作为具有脱酰胺、泛素化和去泛素化活性的独特酶。此外，Lpg 2149通过破坏酶和Ub之间的相互作用直接结合并抑制MavC和MvcA。这些结果为MavC型酶的催化和调节以及这种非经典泛素化机制的分子机制提供了详细的见解。
The bacterial effector MavC catalyzes non-canonical ubiquitination of host E2 enzyme UBE2N without engaging any of the conventional ubiquitination machinery, thereby abolishing UBE2N's function in forming K63-linked ubiquitin (Ub) chains and dampening NF-kB signaling. We now report the structures of MavC in complex with conjugated UBE2N-Ub and an inhibitor protein Lpg2149, as well as the structure of its ortholog, MvcA, bound to Lpg2149. Recognition of UBE2N and Ub depends on several unique features of MavC, which explains the inability of MvcA to catalyze ubiquitination. Unexpectedly, MavC and MvcA also possess deubiquitinase activity against MavC-mediated ubiquitination, highlighting MavC as a unique enzyme possessing deamidation, ubiquitination, and deubiquitination activities. Further, Lpg2149 directly binds and inhibits both MavC and MvcA by disrupting the interactions between enzymes and Ub. These results provide detailed insights into catalysis and regulation of MavC-type enzymes and the molecular mechanisms of this non-canonical ubiquitination machinery.