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Structure paper

TitleDisassembly activates Retron-Septu for antiphage defense.
Journal, issue, pagesScience, Vol. 389, Issue 6762, Page eadv3344, Year 2025
Publish dateAug 21, 2025
AuthorsChen Wang / Anthony D Rish / Emily G Armbruster / Jiale Xie / Anna B Loveland / Zhangfei Shen / Bradley Gu / Andrei A Korostelev / Joe Pogliano / Tian-Min Fu /
PubMed AbstractRetrons 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.
External linksScience / PubMed:40504952 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.47 Å
Structure data

47737

9e8z

EMDB-47737, PDB-9e8z:
4-component structure of retron Ec83
Method: EM (single particle) / Resolution: 3.47 Å

47738

9e90

EMDB-47738, PDB-9e90:
Ec83 Retron PtuA/PtuB (2-1) complex bound to ATP
Method: EM (single particle) / Resolution: 3.45 Å

47739

9e91

EMDB-47739, PDB-9e91:
Ec83 Retron PtuA Dimer bound to ATP
Method: EM (single particle) / Resolution: 3.31 Å

EMDB-47740: Retron Ec78 cryo-EM map at 3.01 A
Method: EM (single particle) / Resolution: 3.01 Å

70091

9o4a

EMDB-70091, PDB-9o4a:
Ec83 Retron PtuAB mutant complex
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-ZN:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

Source
  • escherichia coli (E. coli)
KeywordsANTIVIRAL PROTEIN / ATPase / HNH-Endonuclease / Retron / msDNA / Dimer / IMMUNE SYSTEM / PtuA / PtuB / HNH nuclease

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