PMID:26395283

Citation	Alawneh, AM, Qi, D, Yonesaki, T and Otsuka, Y (2016) An ADP-ribosyltransferase Alt of bacteriophage T4 negatively regulates the Escherichia coli MazF toxin of a toxin-antitoxin module. Mol. Microbiol. 99:188-98
Abstract	Prokaryotic toxin-antitoxin (TA) systems are linked to many roles in cell physiology, such as plasmid maintenance, stress response, persistence and protection from phage infection, and the activities of toxins are tightly regulated. Here, we describe a novel regulatory mechanism for a toxin of Escherichia coli TA systems. The MazF toxin of MazE-MazF, which is one of the best characterized type II TA systems, was modified immediately after infection with bacteriophage T4. Mass spectrometry demonstrated that the molecular weight of this modification was 542 Da, corresponding to a mono-ADP-ribosylation. This modification disappeared in cells infected with T4 phage lacking Alt, which is one of three ADP-ribosyltransferases encoded by T4 phage and is injected together with phage DNA upon infection. In vivo and in vitro analyses confirmed that T4 Alt ADP-ribosylated MazF at an arginine residue at position 4. Finally, the ADP-ribosylation of MazF by Alt resulted in the reduction of MazF RNA cleavage activity in vitro, suggesting that it may function to inactivate MazF during T4 infection. This is the first example of the chemical modification of an E. coli toxin in TA systems to regulate activity.
Links	PubMed Online version:10.1111/mmi.13225
Keywords	ADP Ribose Transferases/metabolism; Bacteriophage T4/enzymology; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/metabolism; Endoribonucleases/chemistry; Endoribonucleases/metabolism; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli/virology; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/metabolism; Gene Expression Regulation, Bacterial; Host-Parasite Interactions; Molecular Weight; Protein Processing, Post-Translational
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
BPT4:ALT		GO:0018120: peptidyl-arginine ADP-ribosylation	ECO:0000315:		P		Figure 4. WT MazF is ADP ribosylated after WT T4 phage infection but not after Δalt mutant T4 phage infection, indicating that Alt is an ADP-ribosylase. WT MazF with an arginine at position 4 (R4) is ADP-ribosylated while MazF R4A, where R4 has been replaced by alanine, is not ADP-ribosylated after WT T4 phage infection, indicating that R4 is the amino acid ribosylated by Alt.	complete CACAO 13296

References

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