载脂蛋白B mRNA编辑酶催化多肽样蛋白3B赖氨酸残基对于DNA胞嘧啶脱氨基作用、HIV-1限制及核定位并非必需。
APOBEC3B lysine residues are dispensable for DNA cytosine deamination, HIV-1 restriction, and nuclear localization.
作者信息
Molan Amy M, Hanson Heather M, Chweya Cynthia M, Anderson Brett D, Starrett Gabriel J, Richards Christopher M, Harris Reuben S
机构信息
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Howard Hughes Medical Institute, University of Minnesota, Minneapolis, MN 55455, USA.
出版信息
Virology. 2017 Nov;511:74-81. doi: 10.1016/j.virol.2017.08.025. Epub 2017 Aug 23.
The APOBEC3 DNA cytosine deaminase family comprises a fundamental arm of the innate immune response and is best known for retrovirus restriction. Several APOBEC3 enzymes restrict HIV-1 and related retroviruses by deaminating viral cDNA cytosines to uracils compromising viral genomes. Human APOBEC3B (A3B) shows strong virus restriction activities in a variety of experimental systems, and is subjected to tight post-translational regulation evidenced by cell-specific HIV-1 restriction activity and active nuclear import. Here we ask whether lysines and/or lysine post-translational modifications are required for these A3B activities. A lysine-free derivative of human A3B was constructed and shown to be indistinguishable from the wild-type enzyme in DNA cytosine deamination, HIV-1 restriction, and nuclear localization activities. However, lysine loss did render the protein resistant to degradation by SIV Vif. Taken together, we conclude that lysine side chains and modifications thereof are unlikely to be central to A3B function or regulation in human cells.
载脂蛋白B mRNA编辑酶催化多肽样3（APOBEC3）DNA胞嘧啶脱氨酶家族是先天免疫反应的一个基本组成部分，以逆转录病毒限制而闻名。几种APOBEC3酶通过将病毒cDNA胞嘧啶脱氨为尿嘧啶来破坏病毒基因组，从而限制HIV-1和相关逆转录病毒。人类APOBEC3B（A3B）在多种实验系统中表现出强大的病毒限制活性，并受到严格的翻译后调控，细胞特异性HIV-1限制活性和活跃的核输入证明了这一点。在这里，我们探讨这些A3B活性是否需要赖氨酸和/或赖氨酸翻译后修饰。构建了一种无赖氨酸的人类A3B衍生物，结果表明其在DNA胞嘧啶脱氨、HIV-1限制和核定位活性方面与野生型酶没有区别。然而，赖氨酸缺失确实使该蛋白对猴免疫缺陷病毒（SIV）Vif介导的降解具有抗性。综上所述，我们得出结论，赖氨酸侧链及其修饰不太可能是人类细胞中A3B功能或调控的核心因素。
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