Prokaryotic ubiquitin-like protein
| Pup-like protein family | |||||||||
|---|---|---|---|---|---|---|---|---|---|
|
Three Prokaryotic ubiquitin-like proteins (blue) attached to proteasomal ATPase Mpa (red) | |||||||||
| Identifiers | |||||||||
| Symbol | Pup/Mpa PDB:3M9D | ||||||||
| Pfam | PF05639 | ||||||||
| |||||||||
Prokaryotic ubiquitin-like protein (Pup) is a functional analog of ubiquitin found in the prokaryote Mycobacterium tuberculosis.[1] 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[2] 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 (PDB: 3M9D) was first determined by scientists Tao Wang and Huilin Li of the Brookhaven National Laboratory.[3]
The Pup gene encodes a 64–amino acid protein with a molecular size of 6.944 kDa:
| MAQEQTKRGGGGGDDDDIAGSTAAGQERREKLTEETDDLLDEIDDVLEENAEDFVRAYVQKGGQ[4] |
In 2017, the presence of Pup homologs in bacterial species outside of the group of gram-positive bacteria was reported[5]. 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[5]. 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:
| MPTTEQGQKNKQMIPSPGPGGGSGPGPQAPKVEKPNTEEILKRMRKVDPDQARRYRQRTGE[6] |
See also
References
- ↑ 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. PMC 2698935
. PMID 18832610. doi:10.1126/science.1163885. - ↑ 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.
- ↑ http://www.bnl.gov/newsroom/news.php?a=11221
- ↑ http://www.uniprot.org/uniprot/P9WHN4#section_seq
- 1 2 Lehmann, G; Udasin, R.G.; Livneh, I.; Ciechanover, A. (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.". Biochem Biophys Res Commun. 483 (3): 946–950. PMID 28087277. doi:10.1016/j.bbrc.2017.01.037.
- ↑ https://www.ncbi.nlm.nih.gov/protein/WP_048810198.1
External links
- PupDB, a database of pupylated proteins and pupylation sites.