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Title: Three Dimensional Structure of the MqsR:MqsA Complex: a Novel TA Pair Comprised of a Toxin Homologous to RelE and an Antitoxin with Unique Properties

Abstract

One mechanism by which bacteria survive environmental stress is through the formation of bacterial persisters, a sub-population of genetically identical quiescent cells that exhibit multidrug tolerance and are highly enriched in bacterial toxins. Recently, the Escherichia coli gene mqsR (b3022) was identified as the gene most highly upregulated in persisters. Here, we report multiple individual and complex three-dimensional structures of MqsR and its antitoxin MqsA (B3021), which reveal that MqsR:MqsA form a novel toxin:antitoxin (TA) pair. MqsR adopts an alpha/beta fold that is homologous with the RelE/YoeB family of bacterial ribonuclease toxins. MqsA is an elongated dimer that neutralizes MqsR toxicity. As expected for a TA pair, MqsA binds its own promoter. Unexpectedly, it also binds the promoters of genes important for E. coli physiology (e.g., mcbR, spy). Unlike canonical antitoxins, MqsA is also structured throughout its entire sequence, binds zinc and coordinates DNA via its C- and not N-terminal domain. These studies reveal that TA systems, especially the antitoxins, are significantly more diverse than previously recognized and provide new insights into the role of toxins in maintaining the persister state.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Org.:
DOE - OFFICE OF SCIENCE
OSTI Identifier:
1020163
Report Number(s):
BNL-96013-2011-JA
TRN: US201116%%143
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
PLoS Pathogens
Additional Journal Information:
Journal Volume: 5; Journal Issue: 12
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; ANTITOXINS; BACTERIA; DIMERS; DNA; ESCHERICHIA COLI; GENES; PHYSIOLOGY; PROMOTERS; RNA-ASE; TOLERANCE; TOXICITY; TOXINS; ZINC; national synchrotron light source

Citation Formats

Brown, B, Grigoriu, S, Kim, Y, Arruda, J, Davenport, A, wood, T, Peti, W, and Page, R. Three Dimensional Structure of the MqsR:MqsA Complex: a Novel TA Pair Comprised of a Toxin Homologous to RelE and an Antitoxin with Unique Properties. United States: N. p., 2009. Web. doi:10.1371/journal.ppat.1000706.
Brown, B, Grigoriu, S, Kim, Y, Arruda, J, Davenport, A, wood, T, Peti, W, & Page, R. Three Dimensional Structure of the MqsR:MqsA Complex: a Novel TA Pair Comprised of a Toxin Homologous to RelE and an Antitoxin with Unique Properties. United States. https://doi.org/10.1371/journal.ppat.1000706
Brown, B, Grigoriu, S, Kim, Y, Arruda, J, Davenport, A, wood, T, Peti, W, and Page, R. 2009. "Three Dimensional Structure of the MqsR:MqsA Complex: a Novel TA Pair Comprised of a Toxin Homologous to RelE and an Antitoxin with Unique Properties". United States. https://doi.org/10.1371/journal.ppat.1000706.
@article{osti_1020163,
title = {Three Dimensional Structure of the MqsR:MqsA Complex: a Novel TA Pair Comprised of a Toxin Homologous to RelE and an Antitoxin with Unique Properties},
author = {Brown, B and Grigoriu, S and Kim, Y and Arruda, J and Davenport, A and wood, T and Peti, W and Page, R},
abstractNote = {One mechanism by which bacteria survive environmental stress is through the formation of bacterial persisters, a sub-population of genetically identical quiescent cells that exhibit multidrug tolerance and are highly enriched in bacterial toxins. Recently, the Escherichia coli gene mqsR (b3022) was identified as the gene most highly upregulated in persisters. Here, we report multiple individual and complex three-dimensional structures of MqsR and its antitoxin MqsA (B3021), which reveal that MqsR:MqsA form a novel toxin:antitoxin (TA) pair. MqsR adopts an alpha/beta fold that is homologous with the RelE/YoeB family of bacterial ribonuclease toxins. MqsA is an elongated dimer that neutralizes MqsR toxicity. As expected for a TA pair, MqsA binds its own promoter. Unexpectedly, it also binds the promoters of genes important for E. coli physiology (e.g., mcbR, spy). Unlike canonical antitoxins, MqsA is also structured throughout its entire sequence, binds zinc and coordinates DNA via its C- and not N-terminal domain. These studies reveal that TA systems, especially the antitoxins, are significantly more diverse than previously recognized and provide new insights into the role of toxins in maintaining the persister state.},
doi = {10.1371/journal.ppat.1000706},
url = {https://www.osti.gov/biblio/1020163}, journal = {PLoS Pathogens},
number = 12,
volume = 5,
place = {United States},
year = {Thu Jan 01 00:00:00 EST 2009},
month = {Thu Jan 01 00:00:00 EST 2009}
}