7omu
From Proteopedia
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==Thermosipho africanus DarTG in complex with ADP-ribose== | ==Thermosipho africanus DarTG in complex with ADP-ribose== | ||
| - | <StructureSection load='7omu' size='340' side='right'caption='[[7omu]]' scene=''> | + | <StructureSection load='7omu' size='340' side='right'caption='[[7omu]], [[Resolution|resolution]] 2.96Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OMU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OMU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7omu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermosipho_africanus Thermosipho africanus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OMU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OMU FirstGlance]. <br> |
| - | </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=7omu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7omu OCA], [https://pdbe.org/7omu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7omu RCSB], [https://www.ebi.ac.uk/pdbsum/7omu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7omu ProSAT]</span></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]] 2.96Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</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=7omu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7omu OCA], [https://pdbe.org/7omu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7omu RCSB], [https://www.ebi.ac.uk/pdbsum/7omu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7omu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DARTG_THEA7 DARTG_THEA7] A fusion protein of the toxic and antitoxin components of a hybrid type II/IV toxin-antitoxin (TA) system. The N-terminal domain ADP-ribosylates ssDNA on a thymidine residue, while the C-terminal domain removes the modification, neutralizing the toxic effect.[UniProtKB:O53604][UniProtKB:O53605] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | ADP-ribosyltransferases use NAD(+) to catalyse substrate ADP-ribosylation(1), and thereby regulate cellular pathways or contribute to toxin-mediated pathogenicity of bacteria(2-4). Reversible ADP-ribosylation has traditionally been considered a protein-specific modification(5), but recent in vitro studies have suggested nucleic acids as targets(6-9). Here we present evidence that specific, reversible ADP-ribosylation of DNA on thymidine bases occurs in cellulo through the DarT-DarG toxin-antitoxin system, which is found in a variety of bacteria (including global pathogens such as Mycobacterium tuberculosis, enteropathogenic Escherichia coli and Pseudomonas aeruginosa)(10). We report the structure of DarT, which identifies this protein as a diverged member of the PARP family. We provide a set of high-resolution structures of this enzyme in ligand-free and pre- and post-reaction states, which reveals a specialized mechanism of catalysis that includes a key active-site arginine that extends the canonical ADP-ribosyltransferase toolkit. Comparison with PARP-HPF1, a well-established DNA repair protein ADP-ribosylation complex, offers insights into how the DarT class of ADP-ribosyltransferases evolved into specific DNA-modifying enzymes. Together, our structural and mechanistic data provide details of this PARP family member and contribute to a fundamental understanding of the ADP-ribosylation of nucleic acids. We also show that thymine-linked ADP-ribose DNA adducts reversed by DarG antitoxin (functioning as a noncanonical DNA repair factor) are used not only for targeted DNA damage to induce toxicity, but also as a signalling strategy for cellular processes. Using M. tuberculosis as an exemplar, we show that DarT-DarG regulates growth by ADP-ribosylation of DNA at the origin of chromosome replication. | ||
| + | |||
| + | Molecular basis for DarT ADP-ribosylation of a DNA base.,Schuller M, Butler RE, Ariza A, Tromans-Coia C, Jankevicius G, Claridge TDW, Kendall SL, Goh S, Stewart GR, Ahel I Nature. 2021 Aug;596(7873):597-602. doi: 10.1038/s41586-021-03825-4. Epub 2021, Aug 18. PMID:34408320<ref>PMID:34408320</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7omu" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Thermosipho africanus]] | ||
[[Category: Ariza A]] | [[Category: Ariza A]] | ||
Current revision
Thermosipho africanus DarTG in complex with ADP-ribose
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