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| - | ==A PROCESSED NON-CODING RNA REGULATES A BACTERIAL ANTIVIRAL SYSTEM== | + | |
| - | <StructureSection load='2xdd' size='340' side='right' caption='[[2xdd]], [[Resolution|resolution]] 3.20Å' scene=''> | + | ==A processed non-coding RNA regulates a bacterial antiviral system== |
| | + | <StructureSection load='2xdd' size='340' side='right'caption='[[2xdd]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xdd]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Pectobacterium_atrosepticum Pectobacterium atrosepticum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XDD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XDD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2xdd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Pectobacterium_atrosepticum Pectobacterium atrosepticum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XDD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XDD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=A23:ADENOSINE-5-PHOSPHATE-2,3-CYCLIC+PHOSPHATE'>A23</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A23:ADENOSINE-5-PHOSPHATE-2,3-CYCLIC+PHOSPHATE'>A23</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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">[[2xd0|2xd0]], [[2xdb|2xdb]]</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=2xdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xdd OCA], [https://pdbe.org/2xdd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xdd RCSB], [https://www.ebi.ac.uk/pdbsum/2xdd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xdd ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonuclease_T(1) Ribonuclease T(1)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.3 3.1.27.3] </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=2xdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xdd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xdd RCSB], [http://www.ebi.ac.uk/pdbsum/2xdd PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TOXN_PECAT TOXN_PECAT] Toxic component of a type III toxin-antitoxin (TA) system. An endoribonuclease which is active independently of the ribosome, cleaving between the second and third A of AAA(U/G) sequences, although not all occurrences of this tetranucleotide are cleaved (PubMed:23267117). Digests many mRNA species, including its own transcript and its cognate antitoxin RNA ToxI. ToxI has 5.5 nearly identical 36 nucleotide-long repeats (a single repeat neutralizes the toxin in vivo); a single repeat folds into a pseudoknot which binds the toxin (PubMed:21240270). The ToxI precursor RNA is a preferential target in vivo and is progressively degraded to single repeat lengths as ToxN-ToxI complex self-assembly occurs (PubMed:23267117). In vivo expression of ToxI antitoxin inhibits endonuclease activity of ToxN (PubMed:23267117). The toxin alone inhibits growth when expressed in E.coli without causing cell lysis; this bacteriostatic effect is neutralized by cognate RNA antitoxin ToxI (PubMed:19124776, PubMed:23267117). Non-cognate antitoxin RNA from B.thuringiensis does not inhibit this toxin (PubMed:23267117). The RNA antitoxin is less stable than the proteinaceous toxin; synthesis of ToxI in the absence of new ToxN synthesis restores growth and also detectable accumulation of the ToxN protein (PubMed:19124776). Negatively regulates its own operon in complex with ToxI (PubMed:19633081). The toxin-antitoxin system functions in plasmid maintenance (a plasmid addiction system) (PubMed:23267117).<ref>PMID:19124776</ref> <ref>PMID:19633081</ref> <ref>PMID:21240270</ref> <ref>PMID:23267117</ref> The TA system protects P.atrosepticum strain 1043 against phage phiM1 and phiA2, E.coli against some but not all coliphages and S.marcescens against some bacteriophages, causing an abortive infection (Abi phenotype) (PubMed:19124776). Also protects P.atrosepticum strain 1043 against phage phiTE; phage that escape Abi and grow in this bacterium have evolved a pseudo-ToxI RNA by expanding a pre-existing sequence similar to the bona fide ToxI repeats (PubMed:23109916).<ref>PMID:19124776</ref> <ref>PMID:23109916</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2xdd" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Pectobacterium atrosepticum]] | | [[Category: Pectobacterium atrosepticum]] |
| - | [[Category: Blower, T R]] | + | [[Category: Blower TR]] |
| - | [[Category: Fineran, P C]] | + | [[Category: Fineran PC]] |
| - | [[Category: Humphreys, D P]] | + | [[Category: Humphreys DP]] |
| - | [[Category: Luisi, B F]] | + | [[Category: Luisi BF]] |
| - | [[Category: Pei, X Y]] | + | [[Category: Pei XY]] |
| - | [[Category: Salmond, G P.C]] | + | [[Category: Salmond GPC]] |
| - | [[Category: Short, F L]] | + | [[Category: Short FL]] |
| - | [[Category: Abortive infection]]
| + | |
| - | [[Category: Phage]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Toxin-rna complex]]
| + | |
| Structural highlights
Function
TOXN_PECAT Toxic component of a type III toxin-antitoxin (TA) system. An endoribonuclease which is active independently of the ribosome, cleaving between the second and third A of AAA(U/G) sequences, although not all occurrences of this tetranucleotide are cleaved (PubMed:23267117). Digests many mRNA species, including its own transcript and its cognate antitoxin RNA ToxI. ToxI has 5.5 nearly identical 36 nucleotide-long repeats (a single repeat neutralizes the toxin in vivo); a single repeat folds into a pseudoknot which binds the toxin (PubMed:21240270). The ToxI precursor RNA is a preferential target in vivo and is progressively degraded to single repeat lengths as ToxN-ToxI complex self-assembly occurs (PubMed:23267117). In vivo expression of ToxI antitoxin inhibits endonuclease activity of ToxN (PubMed:23267117). The toxin alone inhibits growth when expressed in E.coli without causing cell lysis; this bacteriostatic effect is neutralized by cognate RNA antitoxin ToxI (PubMed:19124776, PubMed:23267117). Non-cognate antitoxin RNA from B.thuringiensis does not inhibit this toxin (PubMed:23267117). The RNA antitoxin is less stable than the proteinaceous toxin; synthesis of ToxI in the absence of new ToxN synthesis restores growth and also detectable accumulation of the ToxN protein (PubMed:19124776). Negatively regulates its own operon in complex with ToxI (PubMed:19633081). The toxin-antitoxin system functions in plasmid maintenance (a plasmid addiction system) (PubMed:23267117).[1] [2] [3] [4] The TA system protects P.atrosepticum strain 1043 against phage phiM1 and phiA2, E.coli against some but not all coliphages and S.marcescens against some bacteriophages, causing an abortive infection (Abi phenotype) (PubMed:19124776). Also protects P.atrosepticum strain 1043 against phage phiTE; phage that escape Abi and grow in this bacterium have evolved a pseudo-ToxI RNA by expanding a pre-existing sequence similar to the bona fide ToxI repeats (PubMed:23109916).[5] [6]
Publication Abstract from PubMed
Various mechanisms exist that enable bacteria to resist bacteriophage infection. Resistance strategies include the abortive infection (Abi) systems, which promote cell death and limit phage replication within a bacterial population. A highly effective 2-gene Abi system from the phytopathogen Erwinia carotovora subspecies atroseptica, designated ToxIN, is described. The ToxIN Abi system also functions as a toxin-antitoxin (TA) pair, with ToxN inhibiting bacterial growth and the tandemly repeated ToxI RNA antitoxin counteracting the toxicity. TA modules are currently divided into 2 classes, protein and RNA antisense. We provide evidence that ToxIN defines an entirely new TA class that functions via a novel protein-RNA mechanism, with analogous systems present in diverse bacteria. Despite the debated role of TA systems, we demonstrate that ToxIN provides viral resistance in a range of bacterial genera against multiple phages. This is the first demonstration of a novel mechanistic class of TA systems and of an Abi system functioning in different bacterial genera, both with implications for the dynamics of phage-bacterial interactions.
The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair.,Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS, Salmond GP Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9. Epub 2009 Jan 5. PMID:19124776[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS, Salmond GP. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9. Epub 2009 Jan 5. PMID:19124776 doi:10.1073/pnas.0808832106
- ↑ Blower TR, Fineran PC, Johnson MJ, Toth IK, Humphreys DP, Salmond GP. Mutagenesis and functional characterization of the RNA and protein components of the toxIN abortive infection and toxin-antitoxin locus of Erwinia. J Bacteriol. 2009 Oct;191(19):6029-39. PMID:19633081 doi:10.1128/JB.00720-09
- ↑ Blower TR, Pei XY, Short FL, Fineran PC, Humphreys DP, Luisi BF, Salmond GP. A processed noncoding RNA regulates an altruistic bacterial antiviral system. Nat Struct Mol Biol. 2011 Feb;18(2):185-90. Epub 2011 Jan 16. PMID:21240270 doi:10.1038/nsmb.1981
- ↑ Short FL, Pei XY, Blower TR, Ong SL, Fineran PC, Luisi BF, Salmond GP. Selectivity and self-assembly in the control of a bacterial toxin by an antitoxic noncoding RNA pseudoknot. Proc Natl Acad Sci U S A. 2012 Dec 24. PMID:23267117 doi:http://dx.doi.org/10.1073/pnas.1216039110
- ↑ Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS, Salmond GP. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9. Epub 2009 Jan 5. PMID:19124776 doi:10.1073/pnas.0808832106
- ↑ Blower TR, Evans TJ, Przybilski R, Fineran PC, Salmond GP. Viral evasion of a bacterial suicide system by RNA-based molecular mimicry enables infectious altruism. PLoS Genet. 2012;8(10):e1003023. PMID:23109916 doi:10.1371/journal.pgen.1003023
- ↑ Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS, Salmond GP. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9. Epub 2009 Jan 5. PMID:19124776 doi:10.1073/pnas.0808832106
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