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Mode of Action (MoA)
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binds toxins (LsoA and RnlA) and neutralises them.
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Evidence
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Dmd of bacteriophage T4 was identified as a broad-spectrum antitoxin through phage infection experiments in E. coli. T4 Δdmd mutants exhibited severely impaired growth on E. coli strains carrying either the chromosomal rnlA-rnlB or the plasmid-encoded lsoA-lsoB toxin-antitoxin (TA) systems (ECO_0001175), implicating Dmd in suppression of both toxins (RnlA and LsoA). In contrast, wild-type T4 grew normally under the same conditions, indicating that Dmd inactivates these host toxins. Co-expression of Dmd rescued the growth defects caused by RnlA and LsoA overexpression in ΔrnlAB strains. Immunoprecipitation (ECO_0005644) and pull-down (ECO_0006249) assays confirmed direct physical interaction between Dmd and the toxins LsoA and RnlA. Upon T4 infection, host antitoxins RnlB and LsoB rapidly degraded, while Dmd accumulated and associated with the toxins, replacing native antitoxins and blocking toxin activity. These results demonstrate that Dmd acts as a protein antitoxin by directly binding and neutralizing multiple non-cognate toxins to promote T4 phage propagation.
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MoA Category
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binds and inhibits host defence system
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Subtype(s) of the defence system(s) inhibited by the protein
Defence Subtype
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Escherichia coli type II TA systems RnlA-RnlB and LsoA-LsoB
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Relevant publication(s)
DOI
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10.1111/j.1365-2958.2012.07975.x
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Other components of the anti-defence system
Multicomponent System
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-
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Known structure in PDB
PDB ID
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5HY3_B
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Genome(s) encoding the protein
Protein Source
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Enterobacteria phage T4
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Defence system(s) inhibited by the protein
Defences
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TA
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