ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.
One way this protein modification can be produced is by NAD+:diphthamide ADP-ribosyltransferase enzymes, which transfer the ADP-ribose group from nicotinamide adenine dinucleotide (NAD+) onto acceptors such as arginine, glutamic acid, or aspartic acid. In humans, one type of ADP-ribosyltransferases is the NAD:arginine ADP-ribosyltransferases, which modify amino acid residues in proteins such as histones by adding a single ADP-ribose group. These reactions are reversible; for example, when arginine is modified, the ADP-ribosylarginine produced can be removed by ADP-ribosylarginine hydrolases.
Multiple groups of ADP-ribose moieties can also be transferred to proteins to form long branched chains, in a reaction called poly(ADP-ribosyl)ation. This protein modification is carried out by the poly ADP-ribose polymerases (PARPs), which are found in most eukaryotes, but not prokaryotes or yeast. The poly(ADP-ribose) structure is involved in the regulation of several cellular events and is most important in the cell nucleus, in processes such as DNA repair and telomere maintenance.
ADP-ribosylation is also responsible for the actions of some bacterial toxins, such as cholera toxin, diphtheria toxin, pertussis toxin, Clostridium botulinum C3 toxin and heat-labile enterotoxin. These toxin proteins are ADP-ribosyltransferases that modify target proteins in human cells. For example, cholera toxin ADP-ribosylates G proteins, causing massive fluid secretion from the lining of the small intestine, resulting in life-threatening diarrhea. P. aeruginosa ADP-ribosylates cytoskeleton and GTP-binding proteins.
Bacteria, including both pathogens and environmental strains, have an enzyme, Arr, which inactivates rifampin by ADP-ribosylation and thus conferring antibiotic resistance.
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