8QBM

Retron-Eco1 filament with ADP-ribosylated Effector (full map with 2 segments)

Summary for 8QBM

• Entry DOI: 10.2210/pdb8qbm/pdb
• EMDB information: 18315
• Descriptor: Retron Ec86 reverse transcriptase, Retron-Eco1-msr, Retron-Eco1-A2, ... (7 entities in total)
• Functional Keywords: retron, n-glycosidase, dna-rna-protein complex, immune system
• Biological source: Escherichia coli BL21(DE3); More
• Total number of polymer chains: 29
• Total formula weight: 762280.07

Authors

Carabias del Rey, A.,Montoya, G. (deposition date: 2023-08-24, release date: 2024-06-05, Last modification date: 2024-11-13)

Primary citation

Carabias, A.,Camara-Wilpert, S.,Mestre, M.R.,Lopez-Mendez, B.,Hendriks, I.A.,Zhao, R.,Pape, T.,Fuglsang, A.,Luk, S.H.,Nielsen, M.L.,Pinilla-Redondo, R.,Montoya, G.
Retron-Eco1 assembles NAD + -hydrolyzing filaments that provide immunity against bacteriophages.
Mol.Cell, 84:2185-, 2024

PubMed 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.

PubMed: 38788717
DOI: 10.1016/j.molcel.2024.05.001

Experimental method

ELECTRON MICROSCOPY (3.09 Å)