title: A common origin for the bacterial toxin-antitoxin systems parD and ccd, suggested by analyses of toxin/target and toxin/antitoxin interactions.
abstract: Bacterial toxin-antitoxin (TA) systems encode two proteins, a potent inhibitor of cell proliferation (toxin) and its specific antidote (antitoxin). Structural data has revealed striking similarities between the two model TA toxins CcdB, a DNA gyrase inhibitor encoded by the ccd system of plasmid F, and Kid, a site-specific endoribonuclease encoded by the parD system of plasmid R1. While a common structural fold seemed at odds with the two clearly different modes of action of these toxins, the possibility of functional crosstalk between the parD and ccd systems, which would further point to their common evolutionary origin, has not been documented. Here, we show that the cleavage of RNA and the inhibition of protein synthesis by the Kid toxin, two activities that are specifically counteracted by its cognate Kis antitoxin, are altered, but not inhibited, by the CcdA antitoxin. In addition, Kis was able to inhibit the stimulation of DNA gyrase-mediated cleavage of DNA by CcdB, albeit less efficiently than CcdA. We further show that physical interactions between the toxins and antitoxins of the different systems do occur and define the stoichiometry of the complexes formed. We found that CcdB did not degrade RNA nor did Kid have any reproducible effect on the tested DNA gyrase activities, suggesting that these toxins evolved to reach different, rather than common, cellular targets.
authors.affiliation: Departament of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Smith
authors.forename: Juan
authors.initials: J
authors.lastname: López-Villarejo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Diago-Navarro
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Mitchenall
authors.forename: Arjan
authors.initials: A
authors.lastname: Barendregt
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Heck
authors.forename: Marc
authors.initials: M
authors.lastname: Lemonnier
authors.forename: Anthony
authors.initials: A
authors.lastname: Maxwell
authors.forename: Ramón
authors.initials: R
authors.lastname: Díaz-Orejas
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D002701:Chloramphenicol / Q000737:chemistry; D053837:DNA Cleavage; D004270:DNA, Circular / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D004795:Enzyme Stability; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D019143:Evolution, Molecular; D008156:Luciferases / Q000096:biosynthesis; D008970:Molecular Weight; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000737:chemistry; D059367:RNA Cleavage; D012329:RNA, Bacterial / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C068355:CcdA protein, Bacteria; C068356:CcdB protein, Plasmid F; C073592:CopT protein, Plasmid R1; D004270:DNA, Circular; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C489746:ParD protein, E coli; D011500:Protein Synthesis Inhibitors; D012329:RNA, Bacterial; D002701:Chloramphenicol; D008156:Luciferases