Summary information and primary citation
- PDB-id
-
8qbm;
DSSR-derived features in text and
JSON formats
- Class
- immune system
- Method
- cryo-EM (3.09 Å)
- Summary
- Retron-eco1 filament with adp-ribosylated effector
(full map with 2 segments)
- Reference
-
Carabias A, Camara-Wilpert S, Mestre MR, Lopez-Mendez B,
Hendriks IA, Zhao R, Pape T, Fuglsang A, Luk SH, Nielsen
ML, Pinilla-Redondo R, Montoya G (2024): "Retron-Eco1
assembles NAD + -hydrolyzing filaments that provide
immunity against bacteriophages." Mol.Cell,
84, 2185. 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<sub>+</sub> 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<sub>+</sub> 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.
