Electrostatic interactions guide substrate recognition of the prokaryotic ubiquitin-like protein ligase PafA.

Pupylation, a post-translational modification found in Mycobacterium tuberculosis and other Actinobacteria, involves the covalent attachment of prokaryotic ubiquitin-like protein (Pup) to lysines on target proteins by the ligase PafA (proteasome accessory factor A). Pupylated proteins, like ubiquitinated proteins in eukaryotes, are recruited for proteasomal degradation. Proteomic studies suggest that hundreds of potential pupylation targets are modified by the sole existing ligase PafA.