title: Amino acid residues crucial for specificity of toxin-antitoxin interactions in the homologous Axe-Txe and YefM-YoeB complexes.
abstract: Toxin-antitoxin complexes are ubiquitous in bacteria. The specificity of interactions between toxins and antitoxins from homologous but non-interacting systems was investigated. Based on molecular modeling, selected amino acid residues were changed to assess which positions were crucial in the specificity of toxin-antitoxin interaction in the related Axe-Txe and YefM-YoeB complexes. No cross-interactions between wild-type proteins were detected. However, a single amino acid substitution that converts a Txe-specific residue to a YoeB-specific residue reduced, but did not abolish, Txe interaction with the Axe antitoxin. Interestingly, this alteration (Txe-Asp83Tyr) promoted functional interactions between Txe and the YefM antitoxin. The interactions between Txe-Asp83Tyr and YefM were sufficiently strong to abolish Txe toxicity and to allow effective corepression by YefM-Txe-Asp83Tyr of the promoter from which yefM-yoeB is expressed. We conclude that Asp83 in Txe is crucial for the specificity of toxin-antitoxin interactions in the Axe-Txe complex and that swapping this residue for the equivalent residue in YoeB relaxes the specificity of the toxin-antitoxin interaction.
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Połom
authors.forename: Lidia
authors.initials: L
authors.lastname: Boss
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Węgrzyn
authors.forename: Finbarr
authors.initials: F
authors.lastname: Hayes
authors.forename: Barbara
authors.initials: B
authors.lastname: Kędzierska
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000992:Antitoxins / Q000737:chemistry* / Q000235:genetics; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity; D016984:Enterococcus faecium / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity; D005798:Genes, Bacterial; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D054730:Protein Interaction Domains and Motifs; D017386:Sequence Homology, Amino Acid
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D046912:Multiprotein Complexes; C484519:YefM protein, E coli; C504245:YoeB protein, E coli
keywords: axe-txe; protein interaction specificity; toxin-antitoxin; yefM-yoeB