2mru
From Proteopedia
Structure of truncated EcMazE-DNA complex
Structural highlights
Function[MAZE_ECOLI] Antitoxin component of a toxin-antitoxin (TA) module. Labile antitoxin that binds to the MazF mRNA interferase toxin and neutralizes its endoribonuclease activity. Is considered to be an 'addiction' molecule as the cell will die in its absence. The endoribonuclease activity (MazF, a toxin) is inhibited by the labile cognate antitoxin MazE. Toxicity results when the levels of MazE decrease in the cell, leading to mRNA degradation. This effect can be rescued by expression of MazE, but after 6 hours in rich medium the overexpression of MazF leads to programmed cell death. Cell growth and viability are not affected when MazF and MazE are coexpressed. Both MazE and MazE-MazF bind to the promoter region of the mazE-mazF operon to inhibit their transcription. Cell death governed by the MazE-MazF and DinJ-YafQ TA modules seems to play a role in biofilm formation, while MazE-MazF is also implicated in cell death in liquid media. Publication Abstract from PubMedToxin-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 approximately 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. Escherichia coli antitoxin MazE as transcription factor: insights into MazE-DNA binding.,Zorzini V, Buts L, Schrank E, Sterckx YG, Respondek M, Engelberg-Kulka H, Loris R, Zangger K, van Nuland NA Nucleic Acids Res. 2015 Jan 30;43(2):1241-56. doi: 10.1093/nar/gku1352. Epub 2015, Jan 6. PMID:25564525[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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