Disassembly activates Retron-Septu for antiphage defense

• 成果类型: Article
• 署名作者: Wang, Chen; Rish, Anthony D.; Armbruster, Emily G.; Xie, Jiale; Loveland, Anna B.; Shen, Zhangfei; Gu, Bradley; Korostelev, Andrei A.; Pogliano, Joe; Fu, Tian-Min
• 署名单位: University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School; University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School; University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School; University System of Ohio; Ohio State University; University of California System; University of California San Diego
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9304
• DOI: 10.1126/science.adv3344
• 发表日期: 2025-08-21
• 关键词: single-stranded-dna; rna linked msdna; reverse-transcriptase; escherichia-coli; bacterial retrons; 5' end; biosynthesis; complex

摘要

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.