The Legionella pneumophila effector MavC induces ubiquitination of the E2 ubiquitin-conjugating enzyme UBE2N by transglutamination, thereby abolishing its function in the synthesis of K63 -type polyubiquitin chains. The inhibition of UBE2N activity creates a conundrum because this E2 enzyme is important in multiple signaling pathways, including some that are important for intracellular L. pneumophila replication. Here, we show that prolonged inhibition of UBE2N activity by MavC restricts intracellular bacterial replication and that the activity of UBE2N is restored by MvcA, an ortholog of MavC (50% identity) with ubiquitin deamidase activity. MvcA functions to deubiquitinate UBE2N-Ub using the same catalytic triad required for its deamidase activity. Structural analysis of the MvcA-UBE2N-Ub complex reveals a crucial role of the insertion domain in MvcA in substrate recognition. Our study establishes a deubiquitination mechanism catalyzed by a deamidase, which, together with MavC, imposes temporal regulation of the activity of UBE2N during L. pneumophila infection.

中文翻译：

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嗜肺军团菌通过脱酰胺酶介导的去泛素化调节UBE2N的活性。

嗜肺军团菌效应子MavC通过转谷氨酰胺化诱导E2泛素结合酶UBE2N的泛素化，从而取消了其在K63型多聚泛素链合成中的功能。对UBE2N活性的抑制产生了一个难题，因为这种E2酶在多种信号通路中很重要，包括一些对于细胞内嗜肺乳杆菌复制很重要的通路。在这里，我们显示了MavC对UBE2N活性的长期抑制会限制细胞内细菌的复制，并且MvcA可以还原UBE2N的活性，MvcA是MavC的直系同源物（具有50％的同源性），具有泛素脱酰胺酶活性。MvcA具有使用其脱酰胺酶活性所需的相同催化三联体对UBE2N-Ub进行泛素化的功能。MvcA-UBE2N-Ub复合体的结构分析揭示了MvcA中插入域在底物识别中的关键作用。我们的研究建立了由脱酰胺酶催化的去泛素化机制，该机制与MavC一起在嗜肺乳杆菌感染期间强加了UBE2N活性的时间调节。