Proteasomes are cylindrical, multisubunit proteases found in eukaryotes, eubacteria, and archaebacteria. Eukaryotic proteasomes come in two sizes, the 20S proteasome and the larger adenosine triphosphate (ATP)-dependent 26S proteasome formed by the 20S proteasome and a regulatory complex. Both 20S and 26S proteasomes can associate with protein complexes that activate peptide hydrolysis and may serve to localize the enzymes within cells.
The 20S proteasome has a cylindrical structure that contains four rings stacked on top of each other. Each ring is composed of seven subunits. The two outer rings contain α subunits that do not have enzymatic activity. The two inner rings are comprised of β subunits, where the proteolytic activities reside. The β subunits possess three major proteolytic activities: a chymotrypsin-like (β5), a trypsin-like (β2), and a caspase-like (β1) activity. These proteolytic activities enable the proteasome to cleave proteins into small peptides, usually 8–12 amino acids in length.
The most important proteasome related component is the 19S regulatory complex, which binds to the 20S proteasome to form the 26S proteasome. The 19S complex also termed PA700 regulates the entry of polyubiquitin labeled proteins into the 20S proteasome and activates the 20S proteasome for protein degradation. In addition to 19S complex, there are at least two other intracellular regulatory complexes, PA28 and PA200, that can also use certain types of peptide substrates as models to activate the 20S proteasomes.