| Structural highlights
Function
[YGIT_ECOLI] Antitoxin component of a 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. Overexpression also increases biofilm formation, perhaps by repressing cspD.[1] [2] [3] Also acts as a transcription factor. Both MqsA and MqsRA bind to the promoter region of the mqsRA operon, inactivating (PubMed:19943910) or activating (PubMed:20105222) transcription. Alone or in complex with MqsR binds to other promoters, inducing mcbR and spy and repressing cspD among others.[4] [5] [6]
Publication Abstract from PubMed
Bacterial cultures, especially biofilms produce a small number of persister cells, a genetically identical sub-population of wild type cells that are metabolically dormant, exhibit multidrug tolerance, and are highly enriched in bacterial toxins. The gene most highly upregulated in E. coli persisters is mqsR, a ribonuclease toxin that, along with mqsA, forms a novel toxin:antitoxin (TA) system. Like all known TA systems, both the MqsR:MqsA complex and MqsA alone regulate their own transcription. Despite the importance of TA systems in persistence and biofilms, very little is known about how TA modules, and antitoxins in particular, bind and recognize DNA at a molecular level. Here, we report the crystal structure of MqsA bound to a 26-bp fragment from the mqsRA promoter. We show that MqsA binds DNA predominantly via its C-terminal helix-turn-helix (HTH) domain, with direct binding of recognition helix residues Asn97 and Arg101 to the DNA major groove. Unexpectedly, the structure also revealed that the MqsA N-terminal domain interacts with the DNA phosphate backbone. This results in a more than 105 degrees rotation of the N-terminal domains between the free and complexed states, an unprecedented rearrangement for an antitoxin. The structure also shows that MqsA bends the DNA by more than 55 degrees in order to achieve symmetrical binding. Finally, using a combination of biochemical and NMR studies, we show that the DNA sequence specificity of MqsA is mediated by direct readout.
Structure of the E. coli antitoxin MQSA (YGIT/B3021) bound to its gene promoter reveals extensive domain rearrangements and the specificity of transcriptional regulation.,Brown BL, Wood TK, Peti W, Page R J Biol Chem. 2010 Nov 9. PMID:21068382[7]
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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Brown BL, Wood TK, Peti W, Page R. Structure of the E. coli antitoxin MQSA (YGIT/B3021) bound to its gene promoter reveals extensive domain rearrangements and the specificity of transcriptional regulation. J Biol Chem. 2010 Nov 9. PMID:21068382 doi:10.1074/jbc.M110.172643
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