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| | ==Crystal structure of Shigella flexneri VapBC toxin-antitoxin complex== | | ==Crystal structure of Shigella flexneri VapBC toxin-antitoxin complex== |
| - | <StructureSection load='3tnd' size='340' side='right' caption='[[3tnd]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='3tnd' size='340' side='right'caption='[[3tnd]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tnd]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/"shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TND OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TND FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tnd]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/"shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TND OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TND FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CP0245, mvpA, stborf2, vapC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 "Shigella paradysenteriae" Weldin 1927]), CP0246, mvpT, vapB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 "Shigella paradysenteriae" Weldin 1927])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CP0245, mvpA, stborf2, vapC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 "Shigella paradysenteriae" Weldin 1927]), CP0246, mvpT, vapB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 "Shigella paradysenteriae" Weldin 1927])</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=3tnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tnd OCA], [http://pdbe.org/3tnd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tnd RCSB], [http://www.ebi.ac.uk/pdbsum/3tnd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tnd ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tnd OCA], [https://pdbe.org/3tnd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tnd RCSB], [https://www.ebi.ac.uk/pdbsum/3tnd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tnd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VAPC_SHIFL VAPC_SHIFL]] Toxic component of a toxin-antitoxin (TA) module. A tRNA-(fMet) endonuclease, it cleaves both charged and uncharged tRNA-(fMet) between positions 38 and 39 at the anticodon stem-loop boundary. Does not cleave tRNA(Met), tRNA(Arg2), tRNA(His), tRNA(Leu), tRNA(Phe) tRNA(Thr1), tRNA(Tyr) or tRNA(Val). Overexpression in E.coli inhibits translation, leads to loss of cell growth and degradation of tRNA(fMet); these effects are neutralized by expression of cognate antitoxin VapB. The VapB/VapC complex probably regulates transcription of its own promoter.<ref>PMID:19400780</ref> <ref>PMID:21502523</ref> Ectopic overexpression in E.coli induces the YoeB toxin, but this is not the cause of VapC toxicity.<ref>PMID:19400780</ref> <ref>PMID:21502523</ref> [[http://www.uniprot.org/uniprot/VAPB_SHIFL VAPB_SHIFL]] Antitoxin component of a toxin-antitoxin (TA) module. Upon expression in E.coli neutralizes the effect of cognate toxin VapC. The VapB/VapC complex probably regulates transcription of its own promoter.<ref>PMID:19400780</ref> <ref>PMID:21502523</ref> | + | [[https://www.uniprot.org/uniprot/VAPC_SHIFL VAPC_SHIFL]] Toxic component of a toxin-antitoxin (TA) module. A tRNA-(fMet) endonuclease, it cleaves both charged and uncharged tRNA-(fMet) between positions 38 and 39 at the anticodon stem-loop boundary. Does not cleave tRNA(Met), tRNA(Arg2), tRNA(His), tRNA(Leu), tRNA(Phe) tRNA(Thr1), tRNA(Tyr) or tRNA(Val). Overexpression in E.coli inhibits translation, leads to loss of cell growth and degradation of tRNA(fMet); these effects are neutralized by expression of cognate antitoxin VapB. The VapB/VapC complex probably regulates transcription of its own promoter.<ref>PMID:19400780</ref> <ref>PMID:21502523</ref> Ectopic overexpression in E.coli induces the YoeB toxin, but this is not the cause of VapC toxicity.<ref>PMID:19400780</ref> <ref>PMID:21502523</ref> [[https://www.uniprot.org/uniprot/VAPB_SHIFL VAPB_SHIFL]] Antitoxin component of a toxin-antitoxin (TA) module. Upon expression in E.coli neutralizes the effect of cognate toxin VapC. The VapB/VapC complex probably regulates transcription of its own promoter.<ref>PMID:19400780</ref> <ref>PMID:21502523</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Shigella paradysenteriae weldin 1927]] | | [[Category: Shigella paradysenteriae weldin 1927]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Boggild, A]] | | [[Category: Boggild, A]] |
| | [[Category: Brodersen, D E]] | | [[Category: Brodersen, D E]] |
| Structural highlights
3tnd is a 8 chain structure with sequence from "shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | CP0245, mvpA, stborf2, vapC ("Shigella paradysenteriae" Weldin 1927), CP0246, mvpT, vapB ("Shigella paradysenteriae" Weldin 1927) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[VAPC_SHIFL] Toxic component of a toxin-antitoxin (TA) module. A tRNA-(fMet) endonuclease, it cleaves both charged and uncharged tRNA-(fMet) between positions 38 and 39 at the anticodon stem-loop boundary. Does not cleave tRNA(Met), tRNA(Arg2), tRNA(His), tRNA(Leu), tRNA(Phe) tRNA(Thr1), tRNA(Tyr) or tRNA(Val). Overexpression in E.coli inhibits translation, leads to loss of cell growth and degradation of tRNA(fMet); these effects are neutralized by expression of cognate antitoxin VapB. The VapB/VapC complex probably regulates transcription of its own promoter.[1] [2] Ectopic overexpression in E.coli induces the YoeB toxin, but this is not the cause of VapC toxicity.[3] [4] [VAPB_SHIFL] Antitoxin component of a toxin-antitoxin (TA) module. Upon expression in E.coli neutralizes the effect of cognate toxin VapC. The VapB/VapC complex probably regulates transcription of its own promoter.[5] [6]
Publication Abstract from PubMed
Toxin-antitoxin (TA) loci are common in archaea and prokaryotes and allow cells to rapidly adapt to changing environmental conditions through release of active regulators of metabolism. Many toxins are endonucleases that target cellular mRNA and tRNAs, while the antitoxins tightly wrap around the toxins to inhibit them under normal circumstances. The antitoxins also bind to operators in the promoter regions of the cognate TA operon and thereby regulate transcription. For enteric vapBC TA loci, the VapC toxins specifically cleave tRNA(fMet) and thus down-regulate protein synthesis. Here, we describe the crystal structure of the intact Shigella flexneri VapBC TA complex, determined to 2.7 A resolution. Both in solution and in the crystal structure, four molecules of each protein combine to form a large and globular hetero-octameric assembly with SpoVT/AbrB-type DNA-binding domains at each end and a total molecular mass of about 100 kDa. The structure gives new insights into the inhibition of VapC toxins by VapB and provides the molecular basis for understanding transcriptional regulation through VapB dimerization.
Crystal Structure of the VapBC Toxin-Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly.,Dienemann C, Boggild A, Winther KS, Gerdes K, Brodersen DE J Mol Biol. 2011 Oct 20. PMID:22037005[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Winther KS, Gerdes K. Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase. Mol Microbiol. 2009 May;72(4):918-30. doi: 10.1111/j.1365-2958.2009.06694.x. Epub, 2009 Apr 14. PMID:19400780 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06694.x
- ↑ Winther KS, Gerdes K. Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7403-7. doi:, 10.1073/pnas.1019587108. Epub 2011 Apr 18. PMID:21502523 doi:http://dx.doi.org/10.1073/pnas.1019587108
- ↑ Winther KS, Gerdes K. Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase. Mol Microbiol. 2009 May;72(4):918-30. doi: 10.1111/j.1365-2958.2009.06694.x. Epub, 2009 Apr 14. PMID:19400780 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06694.x
- ↑ Winther KS, Gerdes K. Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7403-7. doi:, 10.1073/pnas.1019587108. Epub 2011 Apr 18. PMID:21502523 doi:http://dx.doi.org/10.1073/pnas.1019587108
- ↑ Winther KS, Gerdes K. Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase. Mol Microbiol. 2009 May;72(4):918-30. doi: 10.1111/j.1365-2958.2009.06694.x. Epub, 2009 Apr 14. PMID:19400780 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06694.x
- ↑ Winther KS, Gerdes K. Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7403-7. doi:, 10.1073/pnas.1019587108. Epub 2011 Apr 18. PMID:21502523 doi:http://dx.doi.org/10.1073/pnas.1019587108
- ↑ Dienemann C, Boggild A, Winther KS, Gerdes K, Brodersen DE. Crystal Structure of the VapBC Toxin-Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly. J Mol Biol. 2011 Oct 20. PMID:22037005 doi:10.1016/j.jmb.2011.10.024
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