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Structure paper

TitlePhage nuclease-mediated defense activation of the bacterial Retron-Eco7 toxin-antitoxin system.
Journal, issue, pagesNucleic Acids Res, Vol. 53, Issue 21, Year 2025
Publish dateNov 13, 2025
AuthorsZhikang Dai / Chang Liu / Yanjing Wang / Xueting Chen / Xiaofang Fu / Kaiyue Yang / Rui Zhu / Xianyue Jia / Yanke Chen / Pan Tao / Zeyuan Guan / Tingting Zou /
PubMed AbstractRetrons are bacterial antiphage defense systems comprising a reverse transcriptase (RT), a non-coding RNA (ncRNA), and cognate effector proteins. The RT synthesizes multicopy single-stranded DNA ...Retrons are bacterial antiphage defense systems comprising a reverse transcriptase (RT), a non-coding RNA (ncRNA), and cognate effector proteins. The RT synthesizes multicopy single-stranded DNA (msDNA) from the ncRNA template to detect phage invasion. This study focuses on Retron-Eco7, which integrates retron-based sensing with the effector module of Septu-a characterized antiphage system in which the PtuAB complex mediates nuclease-dependent defense. However, the activation mechanism of this hybrid system remains unclear. Here, we determined cryo-electron microscopy structures of the RT-msDNA-PtuAB quaternary complex and the PtuAB binary complex in Retron-Eco7. Structural analyses reveal that the DNA stem-loop of msDNA extensively interacts with PtuA subunits via electrostatic interactions. We establish Retron-Eco7 as a novel toxin-antitoxin system, in which RT-msDNA acts as the antitoxin, directly binding and neutralizing the PtuAB toxin. Furthermore, we identified a phage-encoded flap endonuclease as a trigger for Retron-Eco7 activation, which cleaves msDNA to release the PtuAB toxin. Our findings demonstrate the diversity in bacterial retron defense systems and uncover a novel activation mechanism of the Septu-derived retron toxin-antitoxin system.
External linksNucleic Acids Res / PubMed:41277685 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 3.4 Å
Structure data

65052

9vh1

EMDB-65052, PDB-9vh1:
cryoEM structure of ptuA-ptuB complex in Retron-Eco7 anti-phage system
Method: EM (single particle) / Resolution: 3.4 Å

65064

9vhe

EMDB-65064, PDB-9vhe:
cryoEM structure of retron-Eco7 complex
Method: EM (single particle) / Resolution: 2.5 Å

65070

9vhl

EMDB-65070, PDB-9vhl:
cryoEM structure of retron-Eco7 complex (form II)
Method: EM (single particle) / Resolution: 2.6 Å

Chemicals

ChemComp-ZN:
Unknown entry

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

ChemComp-MG:
Unknown entry

Source
  • escherichia coli (E. coli)
KeywordsDNA BINDING PROTEIN / retron-Eco7 / toxin-antitoxin / DNA BINDING PROTEIN/RNA/DNA / DNA BINDING PROTEIN-RNA-DNA complex

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