National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
1F31AI181575-01
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GR128399
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
T32GM144293
米国
引用
ジャーナル: Science / 年: 2025 タイトル: Disassembly activates Retron-Septu for antiphage defense. 著者: Chen Wang / Anthony D Rish / Emily G Armbruster / Jiale Xie / Anna B Loveland / Zhangfei Shen / Bradley Gu / Andrei A Korostelev / Joe Pogliano / Tian-Min Fu / 要旨: Retrons are antiphage defense systems that produce multicopy single-stranded DNA (msDNA) and hold promise for genome engineering. However, the mechanisms of defense remain unclear. The Retron-Septu ...Retrons are antiphage defense systems that produce multicopy single-stranded DNA (msDNA) and hold promise for genome engineering. However, the mechanisms of defense remain unclear. The Retron-Septu system integrates retron and Septu antiphage defenses. Cryo-electron microscopy structures reveal asymmetric nucleoprotein complexes comprising a reverse transcriptase, msDNA (a hybrid of msdDNA and msrRNA), and two PtuAB copies. msdDNA and msrRNA are essential for assembling this complex, with msrRNA adopting a conserved lariat-like structure that regulates reverse transcription. Notably, the assembled Retron-Septu complex is inactive, with msdDNA occupying the PtuA DNA binding site. Activation occurs upon disassembly, releasing PtuAB, which degrades single-stranded DNA to restrict phage replication. This "arrest-and-release" mechanism underscores the dynamic regulatory roles of msDNA, advancing our understanding of antiphage defense strategies.