Escherichia coli antitoxin MazE as transcription factor: insights into MazE-DNA binding

Valentina Zorzini, Lieven Buts, Evelyne Schrank, Yann Sterckx, Michal Respondek, Hanna Engelberg-Kulka, Remy Loris, Klaus Zangger, Nico Van Nuland

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

oxin-antitoxin (TA) modules are pairs of genes essential for bacterial regulation upon environmental stresses. The mazEF module encodes the MazF toxin and its cognate MazE antitoxin. The highly dynamic MazE possesses an N-terminal DNA binding domain through which it can negatively regulate its own promoter. Despite being one of the first TA systems studied, transcriptional regulation of Escherichia coli mazEF remains poorly understood. This paper presents the solution structure of C-terminal truncated E. coli MazE and a MazE-DNA model with a DNA palindrome sequence about 10 bp upstream of the mazEF promoter. The work has led to a transcription regulator-DNA model, which has remained elusive thus far in the E. coli toxin-antitoxin family. Multiple complementary techniques including NMR, SAXS and ITC show that the long intrinsically disordered C-termini in MazE, required for MazF neutralization, does not affect the interactions between the antitoxin and its operator. Rather, the MazE C-terminus plays an important role in the MazF binding, which was found to increase the MazE affinity for the palindromic single site operator.
Original languageEnglish
Pages (from-to)1241-1256
Number of pages16
JournalNucleic Acids Res
Volume43
DOIs
Publication statusPublished - 2015

Keywords

  • Bacterial stress response
  • Bio-SAXS
  • Persister
  • Persistence
  • Protein-DNA interaction
  • Protein-DNA complex
  • NMR spectroscopy

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