Retron-Eco1 assembles NAD+-hydrolyzing filaments that provide immunity against bacteriophages
Research output: Contribution to journal › Journal article › Research › peer-review
Retrons are toxin-antitoxin systems protecting bacteria against bacteriophages via abortive infection. The Retron-Eco1 antitoxin is formed by a reverse transcriptase (RT) and a non-coding RNA (ncRNA)/multi-copy single-stranded DNA (msDNA) hybrid that neutralizes an uncharacterized toxic effector. Yet, the molecular mechanisms underlying phage defense remain unknown. Here, we show that the N-glycosidase effector, which belongs to the STIR superfamily, hydrolyzes NAD+ during infection. Cryoelectron microscopy (cryo-EM) analysis shows that the msDNA stabilizes a filament that cages the effector in a low-activity state in which ADPr, a NAD+ hydrolysis product, is covalently linked to the catalytic E106 residue. Mutations shortening the msDNA induce filament disassembly and the effector's toxicity, underscoring the msDNA role in immunity. Furthermore, we discovered a phage-encoded Retron-Eco1 inhibitor (U56) that binds ADPr, highlighting the intricate interplay between retron systems and phage evolution. Our work outlines the structural basis of Retron-Eco1 defense, uncovering ADPr's pivotal role in immunity.
Original language | English |
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Journal | Molecular Cell |
Volume | 84 |
Issue number | 11 |
Pages (from-to) | 2185-2202.e12 |
Number of pages | 31 |
ISSN | 1097-2765 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:
© 2024 Elsevier Inc.
- ADP-ribosylation, bacteria anti-phage defense, bacterial immune systems, biochemistry, cryoelectron microscopy, Ec86, enzyme mechanisms, NAD, Retron-Eco1, structural biology
Research areas
ID: 394479163