Prokaryotic ubiquitin-like protein
|Pup-like protein family|
Three Prokaryotic ubiquitin-like proteins (blue) attached to proteasomal ATPase Mpa (red)
Prokaryotic ubiquitin-like protein (Pup) is a functional analog of ubiquitin found in the prokaryote Mycobacterium tuberculosis. It serves the same function as ubiquitin, although the enzymology of ubiquitylation and pupylation is different. In contrast to the three-step reaction of ubiquitylation, pupylation requires two steps, therefore only two enzymes are involved in pupylation. Similar to ubiquitin, Pup attaches to specific lysine residues of substrate proteins by forming isopeptide bonds. It is then recognized by Mycobacterium proteasomal ATPase (Mpa) by a binding-induced folding mechanism that forms a unique alpha-helix. Mpa then delivers the Pup-substrate to the 20S proteasome by coupling of ATP hydrolysis for proteasomal degradation.
The discovery of Pup indicates that like eukaryotes, bacteria may use a small-protein modifier to control protein stability.
- Pearce, M. J.; Mintseris, J.; Ferreyra, J.; Gygi, S. P.; Darwin, K. H. (2008). "Ubiquitin-Like Protein Involved in the Proteasome Pathway of Mycobacterium tuberculosis". Science. 322 (5904): 1104–1107. doi:10.1126/science.1163885. PMC . PMID 18832610.
- Wang T, Darwin KH, Li H. Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation.Nat Struct Mol Biol. 2010 Nov;17(11):1352-7. doi: 10.1038/nsmb.1918.
- PupDB, a database of pupylated proteins and pupylation sites.