| Structural highlights
Function
[MQSA_ECOLI] Antitoxin component of a type II toxin-antitoxin (TA) module. Labile antitoxin that binds to the MqsR mRNA interferase toxin and neutralizes its endoribonuclease activity. Overexpression prevents MqsR-mediated cessation of cell growth and inhibition of cell proliferation. Initially reported to act as a cotranscription factor with MqsA (PubMed:19690171, PubMed:20105222). Following further experiments, the MqsR-MqsA complex does not bind DNA and all reported data are actually due to a small fraction of free MqsA alone binding DNA. Addition of MqsR to a preformed MqsA-promoter DNA complex causes dissociation of the MqsA-DNA complex, probably causing derepression of MqsA-repressed transcripts (PubMed:23172222). MqsA binds to 2 palindromes in the promoter region of the mqsRA operon activating its transcription. Binds to other promoters, inducing mcbR and spy and repressing cspD among others (PubMed:20105222). Binds to and represses the rpoS promoter, the master stress regulator, resulting in decreased cyclic-di-GMP, reduced stress resistance, increased cell motility and decreased biofilm formation; in these experiments 5 TA modules are missing (lacks MazEF, RelEB, ChpB, YoeB-YefM, YafQ-DinJ) (PubMed:21516113). An earlier study showed overexpression alone increases biofilm formation, perhaps by repressing cspD; in these experiments the 5 TA modules are present (PubMed:20105222). Represses the csgD promoter. In the presence of stress, when this protein is degraded, the promoters it represses are derepressed, leading to biofilm formation (Probable). This TA system mediates cell growth during bile acid deoxycholate stress by degrading mRNA for probable deoxycholate-binding protein YgiS; bile acid detergents such as deoxycholate are important for host defense against bacterial growth in the gall bladder and duodenum (PubMed:25534751).[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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.,Brown BL, Grigoriu S, Kim Y, Arruda JM, Davenport A, Wood TK, Peti W, Page R PLoS Pathog. 2009 Dec;5(12):e1000706. Epub 2009 Dec 24. PMID:20041169[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yamaguchi Y, Park JH, Inouye M. MqsR, a crucial regulator for quorum sensing and biofilm formation, is a GCU-specific mRNA interferase in Escherichia coli. J Biol Chem. 2009 Oct 16;284(42):28746-53. doi: 10.1074/jbc.M109.032904. Epub, 2009 Aug 18. PMID:19690171 doi:http://dx.doi.org/10.1074/jbc.M109.032904
- ↑ Christensen-Dalsgaard M, Jorgensen MG, Gerdes K. Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses. Mol Microbiol. 2010 Jan;75(2):333-48. doi: 10.1111/j.1365-2958.2009.06969.x. Epub, 2009 Nov 25. PMID:19943910 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06969.x
- ↑ Kim Y, Wang X, Zhang XS, Grigoriu S, Page R, Peti W, Wood TK. Escherichia coli toxin/antitoxin pair MqsR/MqsA regulate toxin CspD. Environ Microbiol. 2010 May;12(5):1105-21. doi: 10.1111/j.1462-2920.2009.02147.x., Epub 2010 Jan 26. PMID:20105222 doi:http://dx.doi.org/10.1111/j.1462-2920.2009.02147.x
- ↑ Wang X, Kim Y, Hong SH, Ma Q, Brown BL, Pu M, Tarone AM, Benedik MJ, Peti W, Page R, Wood TK. Antitoxin MqsA helps mediate the bacterial general stress response. Nat Chem Biol. 2011 Jun;7(6):359-66. doi: 10.1038/nchembio.560. Epub 2011 Apr 24. PMID:21516113 doi:http://dx.doi.org/10.1038/nchembio.560
- ↑ Brown BL, Lord DM, Grigoriu S, Peti W, Page R. The Escherichia coli toxin MqsR destabilizes the transcriptional repression complex formed between the antitoxin MqsA and the mqsRA operon promoter. J Biol Chem. 2013 Jan 11;288(2):1286-94. doi: 10.1074/jbc.M112.421008. Epub 2012 , Nov 21. PMID:23172222 doi:http://dx.doi.org/10.1074/jbc.M112.421008
- ↑ Kwan BW, Lord DM, Peti W, Page R, Benedik MJ, Wood TK. The MqsR/MqsA toxin/antitoxin system protects Escherichia coli during bile acid stress. Environ Microbiol. 2015 Sep;17(9):3168-81. doi: 10.1111/1462-2920.12749. Epub, 2015 Feb 14. PMID:25534751 doi:http://dx.doi.org/10.1111/1462-2920.12749
- ↑ Soo VW, Wood TK. Antitoxin MqsA represses curli formation through the master biofilm regulator CsgD. Sci Rep. 2013 Nov 11;3:3186. doi: 10.1038/srep03186. PMID:24212724 doi:http://dx.doi.org/10.1038/srep03186
- ↑ Brown BL, Grigoriu S, Kim Y, Arruda JM, Davenport A, Wood TK, 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. PLoS Pathog. 2009 Dec;5(12):e1000706. Epub 2009 Dec 24. PMID:20041169 doi:10.1371/journal.ppat.1000706
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