Ubiquitin-like protein
Ubiquitin-like proteins (UBLs) are a family of small proteins involved in post-translational modification of other proteins in a cell, usually with a regulatory function. The UBL protein family derives its name from the first member of the class to be discovered, ubiquitin (Ub), best known for its role in regulating protein degradation. Following the discovery of ubiquitin, many additional evolutionarily related members of the group were described, involving parallel regulatory processes and similar chemistry but distinct cellular functions such as autophagy, protein trafficking, [etc].[1]
Structure and distribution
Members of the UBL family are small, non-enzymatic proteins that share a common structure exemplified by ubiquitin, which has 76 amino acid residues arranged into a "beta-grasp" protein fold consisting of four-strand antiparallel beta sheet surrounding an alpha helix. Ubiquitin itself was named for its presence in all known eukaryotic genomes with high sequence similarity; other members of the family are also widespread in eukaryotes and include SUMO (small ubiquitin-like modifier), NEDD8, [etc]. Proteins in which UBL domains are genetically fused to other domains are also common, particularly in plants.[2] Similar proteins can also be found in prokaryotes, such as prokaryotic ubiquitin-like protein (Pup) in mycobacteria, TtuB in Thermus bacteria, and small archaeal modifier proteins (SAMPs) in archaea; although these proteins share the beta-grasp fold and have functions parallel to eukaryotic UBLs, they are much less widespread, their regulatory pathways are much simpler, and they often have multiple cellular functions.[3]
Regulation
Regulation of UBLs in eukaryotes is elaborate but typically parallel for each member of the family, best characterized for ubiquitin itself. The process of ubiquitination is a tightly regulated three-step sequence: activation, performed by ubiquitin-activating enzymes (E1); conjugation, performed by ubiquitin-conjugating enzymes (E2); and ligation, performed by ubiquitin ligases (E3). The result of this process is the formation of a covalent bond between the C-terminus of ubiquitin and a residue (typically a lysine) on the target protein. In polyubiquitination, additional molecules of ubiquitin are attached to the first, connecting the C-terminus of the second ubiquitin to one of the lysine residues on the first. Different regulatory signals may be sent by differences in the length and branching of the ubiquitin chain. Most UBLs have a similar three-step process catalyzed by a distinct set of E1, E2, and E3 enzymes specific to that UBL; despite similar chemistry, there is little cross-talk between UBL pathways.
- http://www.annualreviews.org/doi/abs/10.1146/annurev-biochem-093010-153308?journalCode=biochem (2012)
- http://www.nature.com/nature/journal/v458/n7237/full/nature07958.html (2009)
- https://www.nature.com/articles/nrd3321 (2011)
- http://www.annualreviews.org/doi/abs/10.1146/annurev-biophys-051013-022958?journalCode=biophys (2014)
References
- ^ Shpilka, T.; Mizushima, N.; Elazar, Z. (26 June 2012). "Ubiquitin-like proteins and autophagy at a glance". Journal of Cell Science. 125 (10): 2343–2348. doi:10.1242/jcs.093757.
- ^ Vierstra, R. D. (12 June 2012). "The Expanding Universe of Ubiquitin and Ubiquitin-Like Modifiers". PLANT PHYSIOLOGY. 160 (1): 2–14. doi:10.1104/pp.112.200667.
- ^ Maupin-Furlow, JA (2014). "Prokaryotic ubiquitin-like protein modification". Annual review of microbiology. 68: 155–75. doi:10.1146/annurev-micro-091313-103447. PMID 24995873.