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8QBK

Retron-Eco1 filament with ADP-ribosylated Effector (local map with 1 segment)

Summary for 8QBK
Entry DOI10.2210/pdb8qbk/pdb
EMDB information18313
DescriptorRetron Ec86 putative ribosyltransferase/DNA-binding protein, Retron Ec86 reverse transcriptase, Retron-Eco1 msDNA, ... (7 entities in total)
Functional Keywordsretron, n-glycosidase, dna-rna-protein complex, immune system
Biological sourceEscherichia coli BL21(DE3)
More
Total number of polymer chains20
Total formula weight531554.61
Authors
Carabias del Rey, A.,Montoya, G. (deposition date: 2023-08-24, release date: 2024-06-05, Last modification date: 2024-11-13)
Primary citationCarabias, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.99 Å)
Structure validation

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