Article

Proteasomes

Institut für Biochemie, Charité Universitätsmedizin Berlin, Monbijoustr. 2, 10117 Berlin, Germany.
Essays in Biochemistry (Impact Factor: 4.39). 02/2005; 41(1):31-48. DOI: 10.1042/EB0410031
Source: PubMed

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.

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    • "We treated the cells with MG132, a specific inhibitor of the proteasome, and observed accumulation of CYP6N3, strongly suggesting proteosomal degradation of CYP6N3. The 26S proteasome is a large multiprotein complex comprised of a 20S proteolytic subunit that is capped at both ends by 19S regulatory subunits [20], [21]. Recent studies revealed that the core catalytic complex of the eukaryotic 20S proteasome has at least five different peptidase activities, and the functions of the 19S regulatory complex are recognition of the polyubiquitinated substrate, release of the polyubiquitin chain, and translocation of the unfolded substrate towards the catalytic sites of the 20S proteasome [22], [23]. "
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