Feiyue Cheng, Aici Wu, Zhihua Li, Jing Xu, Xifeng Cao, Haiying Yu, Zhenquan Liu, Rui Wang, Wenyuan Han, Hua Xiang, Ming Li
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引用次数: 0
摘要
原核生物弓形虫(pAgos)为细菌和古细菌提供了抵抗质粒和病毒的免疫力。具有催化活性的 pAgos 利用短寡核苷酸作为导向,直接裂解外来核酸,而缺乏催化残基的非活性 pAgos 则利用非特异性核酸酶等辅助效应物,在检测到外来核酸时引发中止感染。在这里,我们报告了一组独特的具有催化活性的 pAgo 蛋白,它们经常与磷脂酶 D(PLD)家族蛋白结合。有趣的是,它对单链 DNA 病毒的免疫力依赖于 pAgo 的催化中心,而 PLD 蛋白则增强了这种免疫力。我们还发现,该系统可选择性地抑制病毒 DNA 的繁殖,而不会诱发明显的感染中止结果。此外,pAgo 蛋白单独增强了基因编辑,而 PLD 蛋白却意外地抑制了基因编辑。我们的数据突显了具有催化活性的 pAgo 蛋白能够利用辅助蛋白来加强对不同基因入侵者的定向清除,并强调了 PLD 核酸酶参与宿主免疫的趋势。
Catalytically active prokaryotic Argonautes employ phospholipase D family proteins to strengthen immunity against different genetic invaders.
Prokaryotic Argonautes (pAgos) provide bacteria and archaea with immunity against plasmids and viruses. Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids, while inactive pAgos lacking catalytic residues employ auxiliary effectors, such as nonspecific nucleases, to trigger abortive infection upon detection of foreign nucleic acids. Here, we report a unique group of catalytically active pAgo proteins that frequently associate with a phospholipase D (PLD) family protein. We demonstrate that this particular system employs the catalytic center of the associated PLD protein rather than that of pAgo to restrict plasmid DNA, while interestingly, its immunity against a single-stranded DNA virus relies on the pAgo catalytic center and is enhanced by the PLD protein. We also find that this system selectively suppresses viral DNA propagation without inducing noticeable abortive infection outcomes. Moreover, the pAgo protein alone enhances gene editing, which is unexpectedly inhibited by the PLD protein. Our data highlight the ability of catalytically active pAgo proteins to employ auxiliary proteins to strengthen the targeted eradication of different genetic invaders and underline the trend of PLD nucleases to participate in host immunity.