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| | <StructureSection load='6y2q' size='340' side='right'caption='[[6y2q]], [[Resolution|resolution]] 2.99Å' scene=''> | | <StructureSection load='6y2q' size='340' side='right'caption='[[6y2q]], [[Resolution|resolution]] 2.99Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6y2q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y2Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y2Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6y2q]] is a 2 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=6Y2Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y2Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.99Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rnlA, std, yfjN, b2630, JW2611 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=6y2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y2q OCA], [https://pdbe.org/6y2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y2q RCSB], [https://www.ebi.ac.uk/pdbsum/6y2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y2q 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=6y2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y2q OCA], [https://pdbe.org/6y2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y2q RCSB], [https://www.ebi.ac.uk/pdbsum/6y2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y2q ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RNLA_ECOLI RNLA_ECOLI]] Toxic component of a toxin-antitoxin (TA) module. A stable (half-life 27.6 minutes) endoribonuclease that in the absence of cognate antitoxin RnlB causes generalized RNA degradation. Degrades late enterobacteria phage T4 mRNAs, protecting the host against T4 reproduction. Activity is inhibited by cognate antitoxin RnlB and by enterobacteria phage T4 protein Dmd. Targets cyaA mRNA.<ref>PMID:17895580</ref> <ref>PMID:19019153</ref> <ref>PMID:20980243</ref> <ref>PMID:22403819</ref>
| + | [https://www.uniprot.org/uniprot/RNLA_ECOLI RNLA_ECOLI] Toxic component of a toxin-antitoxin (TA) module. A stable (half-life 27.6 minutes) endoribonuclease that in the absence of cognate antitoxin RnlB causes generalized RNA degradation. Degrades late enterobacteria phage T4 mRNAs, protecting the host against T4 reproduction. Activity is inhibited by cognate antitoxin RnlB and by enterobacteria phage T4 protein Dmd. Targets cyaA mRNA.<ref>PMID:17895580</ref> <ref>PMID:19019153</ref> <ref>PMID:20980243</ref> <ref>PMID:22403819</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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Garcia-Rodriguez, G]] | + | [[Category: Garcia-Rodriguez G]] |
| - | [[Category: Loris, R]] | + | [[Category: Loris R]] |
| - | [[Category: Endoribonuclease]]
| + | |
| - | [[Category: Hepn protein]]
| + | |
| - | [[Category: T4 phage denfense]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Toxin-antitoxin system]]
| + | |
| Structural highlights
Function
RNLA_ECOLI Toxic component of a toxin-antitoxin (TA) module. A stable (half-life 27.6 minutes) endoribonuclease that in the absence of cognate antitoxin RnlB causes generalized RNA degradation. Degrades late enterobacteria phage T4 mRNAs, protecting the host against T4 reproduction. Activity is inhibited by cognate antitoxin RnlB and by enterobacteria phage T4 protein Dmd. Targets cyaA mRNA.[1] [2] [3] [4]
Publication Abstract from PubMed
The rnlAB toxin-antitoxin operon from Escherichia coli functions as an anti-phage defense system. RnlA was identified as a member of the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding domain) superfamily of ribonucleases. The activity of the toxin RnlA requires tight regulation by the antitoxin RnlB, the mechanism of which remains unknown. Here we show that RnlA exists in an equilibrium between two different homodimer states: an inactive resting state and an active canonical HEPN dimer. Mutants interfering with the transition between states show that canonical HEPN dimerization via the highly conserved RX4-6H motif is required for activity. The antitoxin RnlB binds the canonical HEPN dimer conformation, inhibiting RnlA by blocking access to its active site. Single-alanine substitutions mutants of the highly conserved R255, E258, R318 and H323 show that these residues are involved in catalysis and substrate binding and locate the catalytic site near the dimer interface of the canonical HEPN dimer rather than in a groove located between the HEPN domain and the preceding TBP-like domain. Overall, these findings elucidate the structural basis of the activity and inhibition of RnlA and highlight the crucial role of conformational heterogeneity in protein function.
Alternative dimerization is required for activity and inhibition of the HEPN ribonuclease RnlA.,Garcia-Rodriguez G, Charlier D, Wilmaerts D, Michiels J, Loris R Nucleic Acids Res. 2021 Jul 9;49(12):7164-7178. doi: 10.1093/nar/gkab513. PMID:34139012[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Otsuka Y, Koga M, Iwamoto A, Yonesaki T. A role of RnlA in the RNase LS activity from Escherichia coli. Genes Genet Syst. 2007 Aug;82(4):291-9. PMID:17895580
- ↑ Iwamoto A, Lemire S, Yonesaki T. Post-transcriptional control of Crp-cAMP by RNase LS in Escherichia coli. Mol Microbiol. 2008 Dec;70(6):1570-8. doi: 10.1111/j.1365-2958.2008.06504.x. Epub, 2008 Oct 23. PMID:19019153 doi:http://dx.doi.org/10.1111/j.1365-2958.2008.06504.x
- ↑ Koga M, Otsuka Y, Lemire S, Yonesaki T. Escherichia coli rnlA and rnlB compose a novel toxin-antitoxin system. Genetics. 2011 Jan;187(1):123-30. doi: 10.1534/genetics.110.121798. Epub 2010 Oct, 26. PMID:20980243 doi:http://dx.doi.org/10.1534/genetics.110.121798
- ↑ Otsuka Y, Yonesaki T. Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA and RnlA toxins. Mol Microbiol. 2012 Feb;83(4):669-81. PMID:22403819
- ↑ Garcia-Rodriguez G, Charlier D, Wilmaerts D, Michiels J, Loris R. Alternative dimerization is required for activity and inhibition of the HEPN ribonuclease RnlA. Nucleic Acids Res. 2021 Jul 9;49(12):7164-7178. doi: 10.1093/nar/gkab513. PMID:34139012 doi:http://dx.doi.org/10.1093/nar/gkab513
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