9VHE

cryoEM structure of retron-Eco7 complex

Summary for 9VHE

• Entry DOI: 10.2210/pdb9vhe/pdb
• EMDB information: 65064
• Descriptor: Retron Ec78 reverse transcriptase, Retron Ec78 probable ATPase, Retron Ec78 putative HNH endonuclease, ... (7 entities in total)
• Functional Keywords: retron-eco7, toxin-antitoxin, dna binding protein/rna/dna, dna binding protein-rna-dna complex
• Biological source: Escherichia coli; More
• Total number of polymer chains: 8
• Total formula weight: 355541.35

Authors

Dai, Z.K.,Wang, Y.J.,Guan, Z.Y.,Zou, T.T. (deposition date: 2025-06-16, release date: 2025-12-31)

Primary citation

Dai, Z.,Liu, C.,Wang, Y.,Chen, X.,Fu, X.,Yang, K.,Zhu, R.,Jia, X.,Chen, Y.,Tao, P.,Guan, Z.,Zou, T.
Phage nuclease-mediated defense activation of the bacterial Retron-Eco7 toxin-antitoxin system.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: 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.

PubMed: 41277685
DOI: 10.1093/nar/gkaf1173

Experimental method

ELECTRON MICROSCOPY (2.5 Å)