{Reference Type}: Journal Article
{Title}: Retron-Eco1 assembles NAD+-hydrolyzing filaments that provide immunity against bacteriophages.
{Author}: Carabias A;Camara-Wilpert S;Mestre MR;Lopéz-Méndez B;Hendriks IA;Zhao R;Pape T;Fuglsang A;Luk SH;Nielsen ML;Pinilla-Redondo R;Montoya G;
{Journal}: Mol Cell
{Volume}: 84
{Issue}: 11
{Year}: 2024 Jun 6
{Factor}: 19.328
{DOI}: 10.1016/j.molcel.2024.05.001
{Abstract}: 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.