Proteosomes are distributed throughout eukaryotic cells at a high concentration and are the primary sites for protein degradation in mammalian cells. Substrate proteins linked to poly-ubiquitin chains are recognized for proteolytic degradation by the proteasome and recycling of ubiquitin monomers by deubiquitinating enzymes.
The 26S Proteasome (~2500 kDa) is a multicatalytic enzyme with a highly ordered structure composed of at least 32 different subunits arranged in two sub-complexes (a 20S core and a 19S regulator). The 20S core (700 kDa) is composed of 4 rings of 28 non-identical subunits (2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits). Proteolysis occurs within the hollow 20S core which can hydrolyze small peptide substrates, short and unstructured polypeptides and occasionally some proteins with hydrophobic or misfolded patches in vitro.