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

TitleEscherichia coli antitoxin MazE as transcription factor: insights into MazE-DNA binding.
Publication TypeJournal Article
Year of Publication2015
AuthorsZorzini, V., L. Buts, E. Schrank, Y. G. J. Sterckx, M. Respondek, H. Engelberg-Kulka, R. Loris, K. Zangger, and N. A. J. van Nuland
JournalNucleic Acids Res
Date Published2015 Jan
KeywordsDNA, Bacterial, DNA-Binding Proteins, Endoribonucleases, Escherichia coli Proteins, Inverted Repeat Sequences, Models, Molecular, Operator Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Transcription Factors

Toxin-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 ∼ 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.

Alternate JournalNucleic Acids Res.
PubMed ID25564525
PubMed Central IDPMC4333400
Research group: