title: Proteasomes.
abstract: The major enzyme system catalysing the degradation of intracellular proteins is the proteasome system. A central inner chamber of the cylinder-shaped 20 S proteasome contains the active site, formed by N-terminal threonine residues. The 20 S proteasomes are extremely inefficient in degrading folded protein substrates and therefore one or two multisubunit 19 S regulatory particles bind to one or both ends of the 20 S proteasome cylinder, forming 26 S and 30 S proteasomes respectively. These regulatory complexes are able to bind proteins marked as proteasome substrates by prior conjugation with polyubiquitin chains, and initiate their unfolding and translocation into the proteolytic chamber of the 20 S proteasome, where they are broken down into peptides of 3-25 amino acids. The polyubiquitin tag is removed from the substrate protein by the deubiquitinating activity of the 19 S regulator complex. Under conditions of an intensified immune response, many eukaryotic cells adapt by replacing standard 20 S proteasomes with immuno-proteasomes and/or generating the proteasome activator complex, PA28. Both of these adaptations change the protein-breakdown process for optimized generation of antigenic peptide epitopes that are presented by the class I MHCs. Hybrid proteasomes (19 S regulator-20 S proteasome-PA28) may have a special function during the immune response. The functions of other proteasome accessory complexes, such as PA200 and PI31 are still under investigation.
authors.affiliation: Institut für Biochemie, Charité Universitätsmedizin Berlin, Monbijoustr. 2, 10117 Berlin, Germany. burkhardt.dahlmann@charite.de
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Dahlmann
mesh_terms: D000818:Animals; D006801:Humans; D008958:Models, Molecular; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D021381:Protein Transport
chemical_list: D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease