A dual role in regulation and toxicity for the disordered N-terminus of the toxin GraT

Nat Commun. 2019 Feb 27;10(1):972. doi: 10.1038/s41467-019-08865-z.


Bacterial toxin-antitoxin (TA) modules are tightly regulated to maintain growth in favorable conditions or growth arrest during stress. A typical regulatory strategy involves the antitoxin binding and repressing its own promoter while the toxin often acts as a co-repressor. Here we show that Pseudomonas putida graTA-encoded antitoxin GraA and toxin GraT differ from other TA proteins in the sense that not the antitoxin but the toxin possesses a flexible region. GraA auto-represses the graTA promoter: two GraA dimers bind cooperatively at opposite sides of the operator sequence. Contrary to other TA modules, GraT is a de-repressor of the graTA promoter as its N-terminal disordered segment prevents the binding of the GraT2A2 complex to the operator. Removal of this region restores operator binding and abrogates Gr aT toxicity. GraTA represents a TA module where a flexible region in the toxin rather than in the antitoxin controls operon expression and toxin activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitoxins / genetics
  • Antitoxins / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism*
  • Bacterial Toxins / toxicity
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • Genes, Bacterial
  • Intrinsically Disordered Proteins / chemistry
  • Intrinsically Disordered Proteins / genetics
  • Intrinsically Disordered Proteins / metabolism
  • Models, Molecular
  • Nucleic Acid Conformation
  • Operon
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Folding
  • Protein Structure, Quaternary
  • Pseudomonas putida / genetics
  • Pseudomonas putida / metabolism
  • Static Electricity
  • Toxin-Antitoxin Systems / genetics


  • Antitoxins
  • Bacterial Proteins
  • Bacterial Toxins
  • DNA, Bacterial
  • Intrinsically Disordered Proteins