9p4k
From Proteopedia
The structure of Retron Eco8-SSB complex
Structural highlights
FunctionOLD8_ECOLX Probable nuclease member of antiviral defense system retron Eco8, composed of an reverse transcriptase (RT), this nuclease and a non-coding RNA (ncRNA) encoded between them. Expression of retron Eco8 confers protection against bacteriophages T4, T6, T7 and SECphi4, SECphi6 and SECphi18. At multiplicity of infection (MOI) of 0.02 cultures slow growth when infected with SECphi4 but do not collapse, at MOI 2 cultures collapse. When the retron is cloned in another E.coli strain synthesizes msDNA (a branched RNA linked by a 2',5'-phosphodiester bond to a single-stranded DNA). The retron transcript serves as primer and template to the reaction, and codes for the RT.[1] Publication Abstract from PubMedRetrons are antiphage defense systems that synthesize multicopy single-stranded DNA (msDNA) and are being adapted for genome engineering. The Escherichia coli retron Eco8 system comprises a reverse transcriptase (RT), an msDNA, and an overcoming lysogenization defect (OLD)-family nuclease (Eco8-OLD), reminiscent of Gabija. Here, we present the cryo-electron microscopy structure of the Eco8 supramolecular complex, a symmetric 4:4:4 assembly of RT, Eco8-OLD, and msDNA (a hybrid of msrRNA and msdDNA). The msDNA anchors RT and Eco8-OLD into a compact architecture that traps Eco8-OLD in an autoinhibited conformation. Upon phage infection, phage single-stranded DNA-binding proteins (SSBs) bind msdDNA, inducing conformational rearrangements that relieve Eco8-OLD autoinhibition and activate its non-specific DNA nuclease activity. This structural transition enables Eco8 to mount a robust antiphage response by restricting phage genome amplification. Our findings reveal a previously unrecognized mechanism of retron activation and highlight the central role of msDNA as a molecular switch in controlling retron-mediated antiphage defense. Phage SSB detection by retron Eco8 msDNA unleashes nuclease-mediated immunity.,Yu C, Wang C, Forman T, Xie J, Major S, Fang MX, Voyer JE, Pogliano J, Fu TM Mol Cell. 2025 Oct 30:S1097-2765(25)00824-X. doi: 10.1016/j.molcel.2025.10.007. PMID:41172989[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Escherichia coli | Large Structures | Fu T | Wang C | Yu C
