Porcine epidemic diarrhea is a devastating porcine disease that is caused by the alphacoronavirus porcine epidemic diarrhea virus (PEDV). Like other members of the Coronaviridae family, PEDV encodes a multifunctional papain-like protease 2 (PLP2) that has the ability to process the coronavirus viral polyprotein to aid in RNA replication and antagonize the host innate immune response through cleavage of the regulatory proteins ubiquitin (Ub) and/or interferon-stimulated gene product 15 (ISG15) (deubiquitination and deISGylation, respectively). Because Betacoronavirus PLPs have been well characterized, it was sought to determine how PLP2 from the alphacoronavirus PEDV differentiates itself from its related counterparts. PEDV PLP2 was first biochemically characterized, and a 3.1 Å resolution crystal structure of PEDV PLP2 bound to Ub was then solved, providing insight into how Alphacoronavirus PLPs bind to their preferred substrate, Ub. It was found that PEDV PLP2 is a deubiquitinase and readily processes a variety of di-Ub linkages, in comparison with its Betacoronavirus counterparts, which have a narrower range of di-Ub activity but process both Ub and ISG15.

中文翻译：

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α冠状病毒猪流行性腹泻病毒中的木瓜蛋白酶2与泛素相互作用的结构见解

猪流行性腹泻是一种毁灭性的猪疾病，由甲型冠状病毒猪流行性腹泻病毒（PEDV）引起。与冠状病毒科的其他成员一样，PEDV 编码一种多功能木瓜蛋白酶样蛋白酶 2 (PLP2)，它能够处理冠状病毒病毒多蛋白，以帮助 RNA 复制，并通过裂解调节蛋白泛素来拮抗宿主先天免疫反应。 Ub)和/或干扰素刺激的基因产物15 (ISG15)（分别是去泛素化和去ISG化）。由于β 冠状病毒PLP 已得到很好的表征，因此我们试图确定来自 α 冠状病毒 PEDV 的 PLP2 如何与其相关对应物区分开来。首先对 PEDV PLP2 进行了生化表征，然后解析了与 Ub 结合的 PEDV PLP2 的 3.1 Å 分辨率晶体结构，从而深入了解Alphacoronavirus PLP 如何与其首选底物 Ub 结合。研究发现，PEDV PLP2 是一种去泛素酶，与Betacoronavirus对应物相比，它很容易处理各种 di-Ub 连接，后者的 di-Ub 活性范围较窄，但同时处理 Ub 和 ISG15。