The E. coli HicB Antitoxin Contains a Structurally Stable Helix-Turn-Helix DNA Binding Domain

Structure. 2019 Nov 5;27(11):1675-1685.e3. doi: 10.1016/j.str.2019.08.008. Epub 2019 Sep 5.


The E. coli hicAB type II toxin-antitoxin locus is unusual by being controlled by two promoters and by having the toxin encoded upstream of the antitoxin. HicA toxins contain a double-stranded RNA-binding fold and cleaves both mRNA and tmRNA in vivo, while HicB antitoxins contain a partial RNase H fold and either a helix-turn-helix (HTH) or ribbon-helix-helix domain. It is not known how an HTH DNA-binding domain affects higher-order structure for the HicAB modules. Here, we present crystal structures of the isolated E. coli HicB antitoxin and full-length HicAB complex showing that HicB forms a stable DNA-binding module and interacts in a canonical way with HicA despite the presence of an HTH-type DNA-binding domain. No major structural rearrangements take place upon binding of the toxin. Both structures expose well-ordered DNA-binding motifs allowing a model for DNA binding by the antitoxin to be generated.

Keywords: DNA-binding protein; RNase H; antitoxin; helix-turn-helix; ribbon-helix-helix; toxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA / chemistry
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Escherichia coli
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Stability
  • Toxin-Antitoxin Systems*


  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • DNA