PROSITE documentation PDOC52018DNA ADP-ribosyl transferase (DarT) domain profile
ADP-ribosylation is a chemical modification of macromolecules via transfer of an ADP-ribose (ADPr) moiety from NAD(+) onto molecular targets (usually proteins). ADP-ribosyltransferases use NAD(+) to catalyse substrate ADP-ribosylation, and thereby regulate cellular pathways or contribute to toxin-mediated pathogenicity of bacteria. Reversible ADP-ribosylation of DNA on thymidine bases occurs 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). The bacterial DNA ADP-ribosyl transferase (DarT) protein is a toxin that has been shown to transfer ADP-ribose from NAD(+) onto thymidine bases present in single-stranded DNA (ssDNA) specifically at the four-base motif TNTC, and to have no activity on RNA or protein targets. DarT is controlled by its antitoxin DarG (for DNA ADP-ribosyl glycohydrolase) that can strip off the ADP-ribosylation and consequently abolish the growth arrest caused by DarT in bacterial cells. In its N-terminal part, DarG contains a so-called macro domain that is well known as a module interacting with-and frequently removing-ADP-ribosylation (see <PDOC51154>), while the C-terminal region of the antitoxin does not display any known protein domains [1,2,3].
The DarT domain contains a fold-stabilizing central six-stranded β-sheet core (see <PDB:7OMZ>). The DNA target is bound within a groove that is highly conserved among members of the DarT family, and lined up with a positive electrostatic surface generated by several basic residues. The nucleotides of the DNA target span the entire groove, with the thymidine targeted for ADP-ribosylation pointing orthogonally to the DNA backbone deep into the active site of DarT. DarT catalyses ADP-ribosylation of DNA by linking ADP-ribose at the nicotinamide (NAM) ribose C1'' to the in-ring nitrogen N3 of the thymidine base [1].
The profile we developed covers the entire DarT domain.
Last update:February 2023 / Profile revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Schuller M. Butler R.E. Ariza A. Tromans-Coia C. Jankevicius G. Claridge T.D.W. Kendall S.L. Goh S. Stewart G.R. Ahel I. |
| Title | Molecular basis for DarT ADP-ribosylation of a DNA base. | |
| Source | Nature 596:597-602(2021). | |
| PubMed ID | 34408320 | |
| DOI | 10.1038/s41586-021-03825-4 |
| 2 | Authors | Harms A. Gerdes K. |
| Title | Back to the Roots: Deep View into the Evolutionary History of ADP-Ribosylation Opened by the DNA-Targeting Toxin-Antitoxin Module DarTG. | |
| Source | Mol. Cell. 64:1020-1021(2016). | |
| PubMed ID | 27984742 | |
| DOI | 10.1016/j.molcel.2016.11.038 |
| 3 | Authors | Jankevicius G. Ariza A. Ahel M. Ahel I. |
| Title | The Toxin-Antitoxin System DarTG Catalyzes Reversible ADP-Ribosylation of DNA. | |
| Source | Mol. Cell. 64:1109-1116(2016). | |
| PubMed ID | 27939941 | |
| DOI | 10.1016/j.molcel.2016.11.014 |
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