NatB 介导的 N 端乙酰化对于甲型流感病毒 PA-X 的关闭活性是必需的。
N-Terminal Acetylation by NatB Is Required for the Shutoff Activity of Influenza A Virus PA-X.
机构信息
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
出版信息
Cell Rep. 2018 Jul 24;24(4):851-860. doi: 10.1016/j.celrep.2018.06.078.
Abstract
N-terminal acetylation is a major posttranslational modification in eukaryotes catalyzed by N-terminal acetyltransferases (NATs), NatA through NatF. Although N-terminal acetylation modulates diverse protein functions, little is known about its roles in virus replication. We found that NatB, which comprises NAA20 and NAA25, is involved in the shutoff activity of influenza virus PA-X. The shutoff activity of PA-X was suppressed in NatB-deficient cells, and PA-X mutants that are not acetylated by NatB showed reduced shutoff activities. We also evaluated the importance of N-terminal acetylation of PA, because PA-X shares its N-terminal sequence with PA. Viral polymerase activity was reduced in NatB-deficient cells. Moreover, mutant PAs that are not acetylated by NatB lost their function in the viral polymerase complex. Taken together, our findings demonstrate that N-terminal acetylation is required for the shutoff activity of PA-X and for viral polymerase activity.
摘要
N 端乙酰化是真核生物中由 N 端乙酰转移酶（NATs）、NatA 到 NatF 催化的主要翻译后修饰。尽管 N 端乙酰化调节多种蛋白质功能，但人们对其在病毒复制中的作用知之甚少。我们发现，包含 NAA20 和 NAA25 的 NatB 参与了流感病毒 PA-X 的关闭活性。NatB 缺陷细胞中的 PA-X 关闭活性受到抑制，而不能被 NatB 乙酰化的 PA-X 突变体显示出降低的关闭活性。我们还评估了 PA N 端乙酰化的重要性，因为 PA-X 与其 N 端序列与 PA 共享。NatB 缺陷细胞中的病毒聚合酶活性降低。此外，不能被 NatB 乙酰化的突变型 PA 失去了其在病毒聚合酶复合物中的功能。总之，我们的研究结果表明，N 端乙酰化对于 PA-X 的关闭活性和病毒聚合酶活性是必需的。
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