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| | ==CdiA-CT from uropathogenic Escherichia coli in complex with cognate immunity protein and CysK== | | ==CdiA-CT from uropathogenic Escherichia coli in complex with cognate immunity protein and CysK== |
| - | <StructureSection load='5j5v' size='340' side='right' caption='[[5j5v]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='5j5v' size='340' side='right'caption='[[5j5v]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5j5v]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J5V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5j5v]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_536 Escherichia coli 536] and [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J5V FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=IT1:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>IT1</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 2.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5j43|5j43]], [[5j4a|5j4a]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cysteine_synthase Cysteine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.47 2.5.1.47] </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=5j5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5v OCA], [https://pdbe.org/5j5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j5v RCSB], [https://www.ebi.ac.uk/pdbsum/5j5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5v ProSAT]</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=5j5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5v OCA], [http://pdbe.org/5j5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j5v RCSB], [http://www.ebi.ac.uk/pdbsum/5j5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5v ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CDII_ECOL5 CDII_ECOL5]] Immunity protein component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system. CDI modules allow bacteria to communicate with and inhibit the growth of closely related neighboring bacteria in a contact-dependent fashion. Protects cells against the tRNA nuclease activity of CdiA, its cognate toxin protein, but not against CdiA from E.coli strain EC93 or D.dadantii strain 3937.<ref>PMID:21085179</ref> <ref>PMID:22333533</ref> <ref>PMID:24889811</ref> [[http://www.uniprot.org/uniprot/CDIA_ECOL5 CDIA_ECOL5]] Toxic component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system. CDI modules allow bacteria to communicate with and inhibit the growth of closely related neighboring bacteria in a contact-dependent fashion (target cell counts decrease 100- to 1000-fold). CdiA toxicity is neutralized by its cognate immunity protein CdiI, but not by CdiI from other bacteria (PubMed:23469034, PubMed:24889811). BamA on the target cells acts as a receptor for intact CdiA (PubMed:23469034). However isolated CdiA-CT is imported in an F-pilus-mediated fashion; CdiA-CT inhibits F-mediated conjugation, probably via its N-terminus (residues 3016-3097), although it is not clear if this is physiologically significant (PubMed:24889811). The C-terminal domain (CT) cleaves within tRNA anticodon loops (PubMed:22333533, PubMed:24889811); this activity is inhibited by cognate CdiI (PubMed:21085179, PubMed:22333533, PubMed:24889811). tRNase activity of CdiA-CT is stimulated by CysK, although the extreme C-terminus (residues 3098-3242) has tRNase activity in the absence of CysK. In vivo CDI toxicity requires CysK (PubMed:22333533, PubMed:24889811). Purified CdiA-CT (residues 3016-3242) inhibits E.coli cell growth when added to cultures alone or in complex with cognate CdiI, growth is inhibited when cognate CdiI is present within the cell but not when a CdiA-CT/CdiI complex is added extracellularly, suggesting CdiA-CT alone but not the CdiA-CT/CdiI complex is imported into the target cell (PubMed:24889811).<ref>PMID:21085179</ref> <ref>PMID:22333533</ref> <ref>PMID:23469034</ref> <ref>PMID:24889811</ref> <ref>PMID:25174572</ref> | + | [https://www.uniprot.org/uniprot/A0A454A691_ECOL5 A0A454A691_ECOL5] |
| | <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: Cysteine synthase]] | + | [[Category: Escherichia coli 536]] |
| - | [[Category: Goulding, C W]] | + | [[Category: Escherichia coli O157:H7]] |
| - | [[Category: Johnson, P M]]
| + | [[Category: Large Structures]] |
| - | [[Category: Morse, R P]] | + | [[Category: Goulding CW]] |
| - | [[Category: Complex]] | + | [[Category: Johnson PM]] |
| - | [[Category: Endonuclease]] | + | [[Category: Morse RP]] |
| - | [[Category: Immunity protein]] | + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
A0A454A691_ECOL5
Publication Abstract from PubMed
Contact-dependent growth inhibition (CDI) is a widespread mechanism of bacterial competition. CDI(+) bacteria deliver the toxic C-terminal region of contact-dependent inhibition A proteins (CdiA-CT) into neighboring target bacteria and produce CDI immunity proteins (CdiI) to protect against self-inhibition. The CdiA-CT(EC536) deployed by uropathogenic Escherichia coli 536 (EC536) is a bacterial toxin 28 (Ntox28) domain that only exhibits ribonuclease activity when bound to the cysteine biosynthetic enzyme O-acetylserine sulfhydrylase A (CysK). Here, we present crystal structures of the CysK/CdiA-CT(EC536) binary complex and the neutralized ternary complex of CysK/CdiA-CT/CdiI(EC536) CdiA-CT(EC536) inserts its C-terminal Gly-Tyr-Gly-Ile peptide tail into the active-site cleft of CysK to anchor the interaction. Remarkably, E. coli serine O-acetyltransferase uses a similar Gly-Asp-Gly-Ile motif to form the "cysteine synthase" complex with CysK. The cysteine synthase complex is found throughout bacteria, protozoa, and plants, indicating that CdiA-CT(EC536) exploits a highly conserved protein-protein interaction to promote its toxicity. CysK significantly increases CdiA-CT(EC536) thermostability and is required for toxin interaction with tRNA substrates. These observations suggest that CysK stabilizes the toxin fold, thereby organizing the nuclease active site for substrate recognition and catalysis. By contrast, Ntox28 domains from Gram-positive bacteria lack C-terminal Gly-Tyr-Gly-Ile motifs, suggesting that they do not interact with CysK. We show that the Ntox28 domain from Ruminococcus lactaris is significantly more thermostable than CdiA-CT(EC536), and its intrinsic tRNA-binding properties support CysK-independent nuclease activity. The striking differences between related Ntox28 domains suggest that CDI toxins may be under evolutionary pressure to maintain low global stability.
Unraveling the essential role of CysK in CDI toxin activation.,Johnson PM, Beck CM, Morse RP, Garza-Sanchez F, Low DA, Hayes CS, Goulding CW Proc Natl Acad Sci U S A. 2016 Aug 30;113(35):9792-7. doi:, 10.1073/pnas.1607112113. Epub 2016 Aug 16. PMID:27531961[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Johnson PM, Beck CM, Morse RP, Garza-Sanchez F, Low DA, Hayes CS, Goulding CW. Unraveling the essential role of CysK in CDI toxin activation. Proc Natl Acad Sci U S A. 2016 Aug 30;113(35):9792-7. doi:, 10.1073/pnas.1607112113. Epub 2016 Aug 16. PMID:27531961 doi:http://dx.doi.org/10.1073/pnas.1607112113
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