3o9x

From Proteopedia

(Difference between revisions)

Revision as of 10:17, 4 August 2016

Structure of the E. coli antitoxin MqsA (YgiT/b3021) in complex with its gene promoter

Structural highlights

3o9x is a 4 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3hi2, 3gn5, 3ga8, 3fmy
Gene:	b3021, JW2989, ygiT (ECOLI)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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^[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, 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o9x"

@@ Line 1: / Line 1: @@
 ==Structure of the E. coli antitoxin MqsA (YgiT/b3021) in complex with its gene promoter==
 <StructureSection load='3o9x' size='340' side='right' caption='[[3o9x]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3o9x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O9X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O9X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3o9x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O9X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O9X FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hi2|3hi2]], [[3gn5|3gn5]], [[3ga8|3ga8]], [[3fmy|3fmy]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b3021, JW2989, ygiT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b3021, JW2989, ygiT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o9x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o9x RCSB], [http://www.ebi.ac.uk/pdbsum/3o9x PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o9x OCA], [http://pdbe.org/3o9x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o9x RCSB], [http://www.ebi.ac.uk/pdbsum/3o9x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o9x ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/YGIT_ECOLI 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.<ref>PMID:19690171</ref> <ref>PMID:20105222</ref> <ref>PMID:19943910</ref>   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.<ref>PMID:19690171</ref> <ref>PMID:20105222</ref> <ref>PMID:19943910</ref>
+[[http://www.uniprot.org/uniprot/MQSA_ECOLI 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).<ref>PMID:19690171</ref> <ref>PMID:19943910</ref> <ref>PMID:20105222</ref> <ref>PMID:21516113</ref> <ref>PMID:23172222</ref> <ref>PMID:25534751</ref> <ref>PMID:24212724</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3o9x" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Escherichia coli]]
+[[Category: Ecoli]]
 [[Category: Brown, B L]]
 [[Category: Page, R]]

3o9x

From Proteopedia

Revision as of 10:17, 4 August 2016

Structure of the E. coli antitoxin MqsA (YgiT/b3021) in complex with its gene promoter

Structural highlights

Function

Publication Abstract from PubMed

References

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