The overall scheme of phosphoribosyl ubiquitination and structures of key effectors. (A) Phospho-ribosyl ubiquitination pathway. SidE family effectors (SidEs) consist of a PDE (phosphodiesterase) domain and a mART (mono ADP ribosyl transferase) domain, which can cause phospho-ribosyl ubiquitination. The mART domain on SidEs transfers the ADP-ribose moiety from NAD+ (nicotinamide adenine dinucleotide) to Arg42 of ubiquitin and generates ADP-ribosylated ubiquitin (ADPR-Ub). The PDE domain then processes the ADPR-Ub. PDE releases the AMP moiety from ADPR-Ub and produces phosphoribosyl ubiquitin (PR-Ub). PR-Ub is transferred to a serine residue on substrate proteins. DupA and DupB are phosphodiesterases that cleave and release PR-Ub from serine residues in the substrate. (B) Structural comparison between the SidE mART domain (PDB ID: 5ZQ5), PARP1 ART (PDB ID: 4DQY), and PARP3 ART domain (PDB ID:4GV4). (C) The structure of the SidE PDE domain (PDB ID:5ZQ5) and human Phosphodiesterase 4B (PDB ID:5OHJ) are compared. (D) Structural comparison of DupA (PDB:6RYB), DupB (PDB:6B7M), and SidE PDE (PDB ID 5ZQ5).
