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. Modification with Pup is called pupylation. Pup 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.
The X-ray crystal structure of the Pup/Mpa complex has been determined.
In 2017, the presence of Pup homologs in bacterial species outside of the group of gram-positive bacteria was reported. The Pup homologs were termed UBact (for Ubiquitin Bacterial), although the distinction has not been proven to be phylogenetically supported by a separate evolutionary origin and is without experimental evidence. UBact is a homolog of Pup, and is found in several phyla of gram-negative bacteria (Pup is found predominantly in the gram-positive bacterial phylum Actinobacteria). Below is the UBact sequence in the bacterium Methylacidiphilum infernorum:
- Pearce MJ, Mintseris J, Ferreyra J, Gygi SP, Darwin KH (November 2008). "Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis". Science. 322 (5904): 1104–7. doi:10.1126/science.1163885. PMC . PMID 18832610.
- Wang T, Darwin KH, Li H (November 2010). "Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation". Nature Structural & Molecular Biology. 17 (11): 1352–7. doi:10.1038/nsmb.1918. PMC . PMID 20953180.
- "Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation". Nature Structural & Molecular Biology. 17 (11): 1352–7. doi:10.1038/nsmb.1918. PMC . PMID 20953180.; Wang T, Darwin KH, Li H (November 2010).
- Lehmann G, Udasin RG, Livneh I, Ciechanover A (February 2017). "Identification of UBact, a ubiquitin-like protein, along with other homologous components of a conjugation system and the proteasome in different gram-negative bacteria". Biochemical and Biophysical Research Communications. 483 (3): 946–950. doi:10.1016/j.bbrc.2017.01.037. PMID 28087277.
- "Ubiquitin-like protein UBact [Methylacidiphilum infernorum]". NCBI Protein.
- PupDB, a database of pupylated proteins and pupylation sites.