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| | ==Crystal structure of the intact E. coli RelBE toxin-antitoxin complex== | | ==Crystal structure of the intact E. coli RelBE toxin-antitoxin complex== |
| - | <StructureSection load='4fxe' size='340' side='right' caption='[[4fxe]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='4fxe' size='340' side='right'caption='[[4fxe]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fxe]] is a 6 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=4FXE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FXE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fxe]] is a 6 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=4FXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FXE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kha|3kha]], [[2kc8|2kc8]], [[2kc9|2kc9]], [[2k29|2k29]]</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=4fxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fxe OCA], [https://pdbe.org/4fxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fxe RCSB], [https://www.ebi.ac.uk/pdbsum/4fxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fxe ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b1564, JW1556, relB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI]), b1563, JW1555, relE ([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=4fxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fxe OCA], [http://pdbe.org/4fxe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fxe RCSB], [http://www.ebi.ac.uk/pdbsum/4fxe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fxe ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RELB_ECOLI RELB_ECOLI]] Antitoxin component of a toxin-antitoxin (TA) module. Counteracts the effect of RelE via direct protein-protein interaction, enabling the reversion of translation inhibition. Also acts as an autorepressor of relBE transcription. DNA-binding and repression is stronger when complexed with corepressor RelE. Increased transcription rate of relBE and activation of relE is consistent with a lower level of RelB in starved cells due to degradation of RelB by protease Lon.<ref>PMID:9767574</ref> <ref>PMID:11274135</ref> <ref>PMID:11717402</ref> <ref>PMID:12123459</ref> <ref>PMID:19707553</ref> Seems to be a principal mediator of cell death in liquid media.<ref>PMID:9767574</ref> <ref>PMID:11274135</ref> <ref>PMID:11717402</ref> <ref>PMID:12123459</ref> <ref>PMID:19707553</ref> [[http://www.uniprot.org/uniprot/RELE_ECOLI RELE_ECOLI]] Toxic component of a toxin-antitoxin (TA) module. A sequence-specific, ribosome-dependent mRNA endoribonuclease that inhibits translation during amino acid starvation (the stringent response). Acts by cleaving mRNA with high codon specificity in the ribosomal A site between positions 2 and 3. The stop codon UAG is cleaved at a fast rate while UAA and UGA are cleaved with intermediate and slow rates. mRNA cleavage can also occur in the ribosomal E site after peptide release from peptidyl-tRNA in the P site as well as on free 30S subunits. Overexpression of RelE results in the inhibition of bacterial growth and a sharp decrease in colony-forming ability which is inhibited by the labile cognate antitoxin RelB. Overexpression also sharply increases persisters (cells that neither grow or die in presence of bactericidal agent and are largely responsible for high levels of biofilm tolerance to antimicrobials). Acts with RelB as a corepressor of relBE transcription.<ref>PMID:9767574</ref> <ref>PMID:11274135</ref> <ref>PMID:11717402</ref> <ref>PMID:12123459</ref> <ref>PMID:12526800</ref> <ref>PMID:19707553</ref> Seems to be a principal mediator of cell death in liquid media.<ref>PMID:9767574</ref> <ref>PMID:11274135</ref> <ref>PMID:11717402</ref> <ref>PMID:12123459</ref> <ref>PMID:12526800</ref> <ref>PMID:19707553</ref> | + | [https://www.uniprot.org/uniprot/RELB_ECOLI RELB_ECOLI] Antitoxin component of a toxin-antitoxin (TA) module. Counteracts the effect of RelE via direct protein-protein interaction, enabling the reversion of translation inhibition. Also acts as an autorepressor of relBE transcription. DNA-binding and repression is stronger when complexed with corepressor RelE. Increased transcription rate of relBE and activation of relE is consistent with a lower level of RelB in starved cells due to degradation of RelB by protease Lon.<ref>PMID:9767574</ref> <ref>PMID:11274135</ref> <ref>PMID:11717402</ref> <ref>PMID:12123459</ref> <ref>PMID:19707553</ref> Seems to be a principal mediator of cell death in liquid media.<ref>PMID:9767574</ref> <ref>PMID:11274135</ref> <ref>PMID:11717402</ref> <ref>PMID:12123459</ref> <ref>PMID:19707553</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Boggild, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Brodersen, D E]] | + | [[Category: Boggild A]] |
| - | [[Category: Sofos, N]] | + | [[Category: Brodersen DE]] |
| - | [[Category: Nuclease]] | + | [[Category: Sofos N]] |
| - | [[Category: Relb]]
| + | |
| - | [[Category: Rele]]
| + | |
| - | [[Category: Ribosome]]
| + | |
| - | [[Category: Stress response]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Toxin-toxin inhibitor complex]]
| + | |
| - | [[Category: Toxin/antitoxin system]]
| + | |
| - | [[Category: Translational control]]
| + | |
| Structural highlights
Function
RELB_ECOLI Antitoxin component of a toxin-antitoxin (TA) module. Counteracts the effect of RelE via direct protein-protein interaction, enabling the reversion of translation inhibition. Also acts as an autorepressor of relBE transcription. DNA-binding and repression is stronger when complexed with corepressor RelE. Increased transcription rate of relBE and activation of relE is consistent with a lower level of RelB in starved cells due to degradation of RelB by protease Lon.[1] [2] [3] [4] [5] Seems to be a principal mediator of cell death in liquid media.[6] [7] [8] [9] [10]
Publication Abstract from PubMed
The bacterial relBE locus encodes a toxin-antitoxin complex in which the toxin, RelE, is capable of cleaving mRNA in the ribosomal A site cotranslationally. The antitoxin, RelB, both binds and inhibits RelE, and regulates transcription through operator binding and conditional cooperativity controlled by RelE. Here, we present the crystal structure of the intact Escherichia coli RelB2E2 complex at 2.8 A resolution, comprising both the RelB-inhibited RelE and the RelB dimerization domain that binds DNA. RelE and RelB associate into a V-shaped heterotetrameric complex with the ribbon-helix-helix (RHH) dimerization domain at the apex. Our structure supports a model in which relO is optimally bound by two adjacent RelB2E heterotrimeric units, and is not compatible with concomitant binding of two RelB2E2 heterotetramers. The results thus provide a firm basis for understanding the model of conditional cooperativity at the molecular level.
The crystal structure of the intact E. coli RelBE toxin-antitoxin complex provides the structural basis for conditional cooperativity.,Boggild A, Sofos N, Andersen KR, Feddersen A, Easter AD, Passmore LA, Brodersen DE Structure. 2012 Oct 10;20(10):1641-8. doi: 10.1016/j.str.2012.08.017. Epub 2012, Sep 13. PMID:22981948[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gotfredsen M, Gerdes K. The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family. Mol Microbiol. 1998 Aug;29(4):1065-76. PMID:9767574
- ↑ Galvani C, Terry J, Ishiguro EE. Purification of the RelB and RelE proteins of Escherichia coli: RelE binds to RelB and to ribosomes. J Bacteriol. 2001 Apr;183(8):2700-3. PMID:11274135 doi:http://dx.doi.org/10.1128/JB.183.8.2700-2703.2001
- ↑ Christensen SK, Mikkelsen M, Pedersen K, Gerdes K. RelE, a global inhibitor of translation, is activated during nutritional stress. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14328-33. Epub 2001 Nov 20. PMID:11717402 doi:http://dx.doi.org/10.1073/pnas.251327898
- ↑ Pedersen K, Christensen SK, Gerdes K. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol Microbiol. 2002 Jul;45(2):501-10. PMID:12123459
- ↑ Kolodkin-Gal I, Verdiger R, Shlosberg-Fedida A, Engelberg-Kulka H. A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation. PLoS One. 2009 Aug 26;4(8):e6785. doi: 10.1371/journal.pone.0006785. PMID:19707553 doi:10.1371/journal.pone.0006785
- ↑ Gotfredsen M, Gerdes K. The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family. Mol Microbiol. 1998 Aug;29(4):1065-76. PMID:9767574
- ↑ Galvani C, Terry J, Ishiguro EE. Purification of the RelB and RelE proteins of Escherichia coli: RelE binds to RelB and to ribosomes. J Bacteriol. 2001 Apr;183(8):2700-3. PMID:11274135 doi:http://dx.doi.org/10.1128/JB.183.8.2700-2703.2001
- ↑ Christensen SK, Mikkelsen M, Pedersen K, Gerdes K. RelE, a global inhibitor of translation, is activated during nutritional stress. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14328-33. Epub 2001 Nov 20. PMID:11717402 doi:http://dx.doi.org/10.1073/pnas.251327898
- ↑ Pedersen K, Christensen SK, Gerdes K. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol Microbiol. 2002 Jul;45(2):501-10. PMID:12123459
- ↑ Kolodkin-Gal I, Verdiger R, Shlosberg-Fedida A, Engelberg-Kulka H. A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation. PLoS One. 2009 Aug 26;4(8):e6785. doi: 10.1371/journal.pone.0006785. PMID:19707553 doi:10.1371/journal.pone.0006785
- ↑ Boggild A, Sofos N, Andersen KR, Feddersen A, Easter AD, Passmore LA, Brodersen DE. The crystal structure of the intact E. coli RelBE toxin-antitoxin complex provides the structural basis for conditional cooperativity. Structure. 2012 Oct 10;20(10):1641-8. doi: 10.1016/j.str.2012.08.017. Epub 2012, Sep 13. PMID:22981948 doi:http://dx.doi.org/10.1016/j.str.2012.08.017
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