monoADPribosylation

Mono-ADP-ribosylation is a reversible post-translational modification in which a single ADP-ribose moiety is transferred from nicotinamide adenine dinucleotide (NAD+) to a target molecule, most often a protein. The reaction is carried out by mono-ADP-ribosyltransferases, a subset of the ADP-ribosyltransferase superfamily. Unlike poly-ADP-ribosylation, MARylation adds only one ADP-ribose and can modulate activity, interactions, localization, or stability of substrates. Targets include various amino acid side chains, with residue preference depending on the enzyme; arginine, serine, aspartate, and glutamate are commonly cited.

Reversal: MARylation is reversible. Specific hydrolases remove the ADP-ribose, restoring the unmodified state. Known families include ARH1 and ARH3 (ADP-ribosylhydrolases) and macrodomain-containing proteins such as MacroD1, MacroD2, and TARG1, though substrate specificities vary and research is ongoing.

Biological roles: In cells, MARylation participates in signaling pathways, the DNA damage response, transcriptional regulation, and stress responses. It also mediates host-pathogen interactions, as some bacterial toxins exploit MARylation to disrupt host processes. In higher organisms, MAR transferases can modulate protein function and interactions in response to cellular cues.

Detection and study: MARylation is detected by specialized antibodies, NAD+ analog probes, and mass spectrometry-based proteomics. The field is rapidly expanding, with ongoing work to map MARylation sites, identify the responsible enzymes, and understand physiological roles.

History: MARylation was first characterized through bacterial toxin studies showing ADP-ribosylation of host proteins, and has since emerged as an intrinsic, dynamic signaling modification in eukaryotes.