University of Iowa, Department of Microbiology and Immunology, Iowa City, IA 52242, USA; These authors contributed equally to this manuscript.
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; These authors contributed equally to this manuscript.
Trends Microbiol. 2018 Jul;26(7):598-610. doi: 10.1016/j.tim.2017.11.011.
Viruses from the Coronaviridae, Togaviridae, and Hepeviridae families all contain genes that encode a conserved protein domain, called a macrodomain; however, the role of this domain during infection has remained enigmatic. The recent discovery that mammalian macrodomain proteins enzymatically remove ADP-ribose, a common post-translation modification, from proteins has led to an outburst of studies describing both the enzymatic activity and function of viral macrodomains. These new studies have defined these domains as de-ADP-ribosylating enzymes, which indicates that these viruses have evolved to counteract antiviral ADP-ribosylation, likely mediated by poly-ADP-ribose polymerases (PARPs). Here, we comprehensively review this rapidly expanding field, describing the structures and enzymatic activities of viral macrodomains, and discussing their roles in viral replication and pathogenesis.
冠状病毒科、披膜病毒科和肝炎病毒科的病毒均含有编码保守蛋白结构域的基因，称为宏结构域；然而，该结构域在感染过程中的作用仍然是个谜。最近的发现表明，哺乳动物宏结构域蛋白可催化去除蛋白质上常见的翻译后修饰——ADP-核糖，这一发现引发了大量研究，描述了病毒宏结构域的酶活性和功能。这些新的研究将这些结构域定义为去 ADP-核糖基酶，这表明这些病毒已经进化到可以对抗抗病毒 ADP-核糖基化，可能是由多聚 ADP-核糖聚合酶 (PARP) 介导的。在这里，我们全面回顾了这个快速发展的领域，描述了病毒宏结构域的结构和酶活性，并讨论了它们在病毒复制和发病机制中的作用。
