7yk3: Difference between revisions

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-'''Unreleased structure'''
-The entry 7yk3 is ON HOLD
+==Crystal structure of DarTG toxin-antitoxin complex from Mycobacterium tuberculosis==
+<StructureSection load='7yk3' size='340' side='right'caption='[[7yk3]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7yk3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YK3 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7yk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yk3 OCA], [https://pdbe.org/7yk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yk3 RCSB], [https://www.ebi.ac.uk/pdbsum/7yk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yk3 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DART_MYCTU DART_MYCTU] Toxic component of the hybrid type II/IV toxin-antitoxin (TA) system DarTG, which plays a crucial role in controlling bacterial growth and bacteriophage infection. Its toxic effect is neutralized by cognate antitoxin DarG (PubMed:27939941). ADP-ribosylates ssDNA, preferentially in the motif TTTW. In case of phage infection, DarT toxin ADP-ribosylates DNA, which inhibits both viral DNA and RNA synthesis and leads to abortive infection (By similarity). Uncontrolled expression of DarT leads to ADP-ribosylation of the origin of chromosomal replication DNA in cells (in vitro the most heavily modified motifs are TTTT/A in the OriC lower strand) and growth arrest (PubMed:34408320). Is very toxic to E.coli, it cannot be expressed in E.coli (PubMed:27939941). Experiments in situ in which antitoxin DarG levels are depleted (similar to overexpression of DarT) lead to cell death; expression of wild-type DarG protein from M.tuberculosis or T.aquaticus restores growth. Cells with decreased levels of DarG are more sensitive to bedaquilline (targets respiration), DNA-damaging drugs (mitomycin C, netropsin) and transcription-targeted drugs (rifabutin and rifampicin). When DarG is depleted, a DNA-damage response is induced and mutability is increased, suggesting ADP-ribosylation of DNA is the toxic effect (PubMed:32634279).[UniProtKB:B7UP20]<ref>PMID:27939941</ref> <ref>PMID:32634279</ref> <ref>PMID:34408320</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+In the DarTG toxin-antitoxin system, the DarT toxin ADP-ribosylates single-stranded DNA (ssDNA), which stalls DNA replication and plays a crucial role in controlling bacterial growth and bacteriophage infection. This toxic activity is reversed by the N-terminal macrodomain of the cognate antitoxin DarG. DarG also binds DarT, but the role of these interactions in DarT neutralization is unknown. Here, we report that the C-terminal domain of DarG (DarG toxin-binding domain [DarG(TBD)]) interacts with DarT to form a 1:1 stoichiometric heterodimeric complex. We determined the 2.2 A resolution crystal structure of the Mycobacterium tuberculosis DarT-DarG(TBD) complex. The comparative structural analysis reveals that DarG(TBD) interacts with DarT at the DarT/ssDNA interaction interface, thus sterically occluding substrate ssDNA binding and consequently inactivating toxin by direct protein-protein interactions. Our data support a unique two-layered DarT toxin neutralization mechanism of DarG, which is important in keeping the toxin molecules in check under normal growth conditions.
-Authors:
+Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited.,Deep A, Singh L, Kaur J, Velusamy M, Bhardwaj P, Singh R, Thakur KG Structure. 2023 Jul 6;31(7):780-789.e4. doi: 10.1016/j.str.2023.04.008. Epub 2023 , May 10. PMID:37167974<ref>PMID:37167974</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7yk3" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
+[[Category: Deep A]]
+[[Category: Kaur J]]
+[[Category: Singh L]]
+[[Category: Thakur KG]]