Manipulation of host ubiquitin signaling is becoming an increasingly apparent evolutionary strategy among bacterial and viral pathogens. By removing host ubiquitin signals, for example, invading pathogens can inactivate immune response pathways and evade detection. The ovarian tumor (OTU) family of deubiquitinases regulates diverse ubiquitin signals in humans. Viral pathogens have also extensively co‐opted the OTU fold to subvert host signaling, but the extent to which bacteria utilize the OTU fold was unknown. We have predicted and validated a set of OTU deubiquitinases encoded by several classes of pathogenic bacteria. Biochemical assays highlight the ubiquitin and polyubiquitin linkage specificities of these bacterial deubiquitinases. By determining the ubiquitin‐bound structures of two examples, we demonstrate the novel strategies that have evolved to both thread an OTU fold and recognize a ubiquitin substrate. With these new examples, we perform the first cross‐kingdom structural analysis of the OTU fold that highlights commonalities among distantly related OTU deubiquitinases.

中文翻译：

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细菌中多种 OTU 去泛素酶的鉴定和表征。


操纵宿主泛素信号传导正在成为细菌和病毒病原体中越来越明显的进化策略。例如，通过去除宿主泛素信号，入侵的病原体可以使免疫反应途径失活并逃避检测。卵巢肿瘤 (OTU) 去泛素酶家族调节人类的多种泛素信号。病毒病原体也广泛利用 OTU 折叠来破坏宿主信号传导，但细菌利用 OTU 折叠的程度尚不清楚。我们预测并验证了一组由几类病原菌编码的 OTU 去泛素酶。生化测定强调了这些细菌去泛素酶的泛素和多泛素连接特异性。通过确定两个例子的泛素结合结构，我们展示了已经进化到既能穿过 OTU 折叠又能识别泛素底物的新策略。通过这些新的例子，我们对 OTU 折叠进行了首次跨界结构分析，突出了关系较远的 OTU 去泛素酶之间的共性。