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

Zorzini, Valentina; Buts, Lieven; Schrank, Evelyne; Sterckx, Yann G. -J.; Respondek, Michal; Engelberg-Kulka, Hanna; Loris, Remy; Zangger, Klaus; van Nuland, Nico A. J.

doi:10.1093/NAR/GKU1352

Title

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

Author

Zorzini, Valentina

Buts, Lieven

Schrank, Evelyne

Sterckx, Yann G. -J.

Respondek, Michal

Engelberg-Kulka, Hanna

Loris, Remy

Zangger, Klaus

van Nuland, Nico A. J.

Abstract

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 similar to 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.

Language

English

Source (journal)

Nucleic acids research. - London

Publication

London : 2015

ISSN

0305-1048

1362-4962

DOI

10.1093/NAR/GKU1352

Volume/pages