3hi2

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==Structure of the N-terminal domain of the E. coli antitoxin MqsA (YgiT/b3021) in complex with the E. coli toxin MqsR (YgiU/b3022)==
==Structure of the N-terminal domain of the E. coli antitoxin MqsA (YgiT/b3021) in complex with the E. coli toxin MqsR (YgiU/b3022)==
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<StructureSection load='3hi2' size='340' side='right' caption='[[3hi2]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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<StructureSection load='3hi2' size='340' side='right'caption='[[3hi2]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3hi2]] 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=3HI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HI2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3hi2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HI2 FirstGlance]. <br>
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</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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fmy|3fmy]], [[3ga8|3ga8]], [[3gn5|3gn5]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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]), b3022, JW2990, mqsR, ygiU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi2 OCA], [https://pdbe.org/3hi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hi2 RCSB], [https://www.ebi.ac.uk/pdbsum/3hi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hi2 ProSAT]</span></td></tr>
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<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=3hi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi2 OCA], [http://pdbe.org/3hi2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hi2 RCSB], [http://www.ebi.ac.uk/pdbsum/3hi2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hi2 ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[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> [[http://www.uniprot.org/uniprot/MQSR_ECOLI MQSR_ECOLI]] Toxic component of a toxin-antitoxin (TA) module. An mRNA interferase which has been reported to be translation-independent (PubMed:19690171, PubMed:19943910) and translation-dependent (PubMed:20041169). Cleavage has been reported to occur on either side of G in the sequence GCU (PubMed:19690171) but also after C in GC(A/U) sequences (PubMed:19943910). There are only 14 genes in E.coli W3110 (and probably also MG1655) that do not have a GCU sequence and thus are resistant to the mRNA interferase activity. Overexpression causes cessation of cell growth and inhibits cell proliferation via inhibition of translation as well as increasing persister cell formation; these effects are overcome by concomitant or subsequent expression of antitoxin MqsA. Overexpression also leads to a dramatic increase in tolerance to the antibiotic ofloxacin.<ref>PMID:19690171</ref> <ref>PMID:19943910</ref> <ref>PMID:20041169</ref> Acts as a cotranscription factor. Both MqsA and MqsRA bind to the promoter region of the mqsRA operon, inactivating (PubMed:19943910) or activating (PubMed:20105222) transcription. In complex with MqsA binds to other promoters, inducing mcbR and spy and repressing cspD among others, playing a role in biofilm formation. Plays a major role in persister cell formation (cells that are antibiotic resistant without genetic change, usually in biofilms), acting via Hha and CspD. AI-2 controlled regulator that controls biofilm formation by inducing motility through the activation of qseBC and csrA. This leads to the activation via the master flagellum regulon flhDC of fliA, motA and crl.<ref>PMID:19943910</ref> <ref>PMID:20105222</ref>
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[https://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>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hi2 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hi2 ConSurf].
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== Publication Abstract from PubMed ==
 
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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.
 
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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<ref>PMID:20041169</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Ecoli]]
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[[Category: Escherichia coli K-12]]
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[[Category: Arruda, J M]]
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[[Category: Large Structures]]
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[[Category: Brown, B L]]
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[[Category: Arruda JM]]
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[[Category: Grigoriu, S]]
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[[Category: Brown BL]]
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[[Category: Page, R]]
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[[Category: Grigoriu S]]
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[[Category: Peti, W]]
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[[Category: Page R]]
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[[Category: B3021]]
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[[Category: Peti W]]
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[[Category: B3022]]
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[[Category: Dna binding protein-toxin complex]]
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[[Category: Mqsa]]
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[[Category: Mqsr]]
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[[Category: Quorum sensing]]
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[[Category: Stress response]]
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[[Category: Toxin-antitoxin system]]
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[[Category: Ygit]]
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[[Category: Ygiu]]
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[[Category: Zn-binding protein]]
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Current revision

Structure of the N-terminal domain of the E. coli antitoxin MqsA (YgiT/b3021) in complex with the E. coli toxin MqsR (YgiU/b3022)

PDB ID 3hi2

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