9jm0
retron Ec86-effector fiber
Structural highlights
FunctionRT86_ECOLX Reverse transcriptase (RT) component of antiviral defense system retron Ec86, composed of a non-coding RNA (ncRNA), a ribosyltransferase/DNA-binding protein and this RT. Expression of the 3-gene retron confers protection against bacteriophage T5. At multiplicity of infection (MOI) of 0.02 cultures grow normally when infected with T5 without collapsing, at MOI 2 cultures enter growth stasis (PubMed:33157039). Responsible for synthesis of msDNA (a branched molecule with RNA linked by a 2',5'-phosphodiester bond to ssDNA). The retron transcript serves as primer (from a conserved internal G residue) and template for the reaction, and codes for the RT (PubMed:10531319, PubMed:2466573). Recognizes only its cognate RNA as a primer template (PubMed:10531319). Overexpression of the ncRNA and RT (without the ribosyltransferase), which leads to increased levels of msDNA, is mutagenic in vivo (PubMed:7885227). This may be due to a mismatch in the msDNA stem which binds and sequesters MutS and/or MutL (Probable).[1] [2] [3] [4] [5] Publication Abstract from PubMedRetrons are a class of multigene antiphage defense systems typically consisting of a retron reverse transcriptase, a non-coding RNA, and a cognate effector. Although triggers for several retron systems have been discovered recently, the complete mechanism by which these systems detect invading phages and mediate defense remains unclear. Here, we focus on the retron Ec86 defense system, elucidating its modes of activation and mechanisms of action. We identified a phage-encoded DNA cytosine methyltransferase (Dcm) as a trigger of the Ec86 system and demonstrated that Ec86 is activated upon multicopy single-stranded DNA (msDNA) methylation. We further elucidated the structure of a tripartite retron Ec86-effector filament assembly that is primed for activation by Dcm and capable of hydrolyzing nicotinamide adenine dinucleotide (NAD(+)). These findings provide insights into the retron Ec86 defense mechanism and underscore an emerging theme of antiphage defense through supramolecular complex assemblies. DNA methylation activates retron Ec86 filaments for antiphage defense.,Wang Y, Wang C, Guan Z, Cao J, Xu J, Wang S, Cui Y, Wang Q, Chen Y, Yin Y, Zhang D, Liu H, Sun M, Jin S, Tao P, Zou T Cell Rep. 2024 Oct 22;43(10):114857. doi: 10.1016/j.celrep.2024.114857. Epub 2024 , Oct 11. PMID:39395169[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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