EMD-18313
Retron-Eco1 filament with ADP-ribosylated Effector (local map with 1 segment)
EMD-18313
Single-particle2.99 Å
![EMD-18313](https://www.ebi.ac.uk/emdb/images/entry/EMD-18313/400_18313.gif)
Map released: 05/06/2024
Last modified: 13/11/2024
Sample Organism:
Escherichia coli BL21(DE3)
Sample: Filamentous assembly of Retron-Eco1 in complex with ADPr, containing RT-msr-msDNA-Effector complex (1 segment)
Fitted models: 8qbk (Avg. Q-score: 0.468)
Deposition Authors: Carabias del Rey A, Montoya G
Sample: Filamentous assembly of Retron-Eco1 in complex with ADPr, containing RT-msr-msDNA-Effector complex (1 segment)
Fitted models: 8qbk (Avg. Q-score: 0.468)
Deposition Authors: Carabias del Rey A, Montoya G
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
Retron-Eco1 assembles NAD + -hydrolyzing filaments that provide immunity against bacteriophages.
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) Mol Cell , 84 , 2185
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
(2024) Mol Cell , 84 , 2185
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.
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.