Immune system, proteasome

Proteasomes of Thermoplasma contain a single type of p subunit but eukaryotic proteasomes contain subunits with at least three distinct substrate preferences.347 M9c They all appear to use the same hydrolytic mechanism but in their substrate specificities they are chymotrypsin-like, peptidylglutamyl-peptide hydrolyzing, branched chain amino acid preferring, and small neutral amino acid preferring based on the P, amino acid residue. In the spleen some of the P subunits of the proteasomes appear to have been replaced by proteins encoded by the major histocompatibility complex of the immune system (Chapter 31).347 This may alter the properties of the proteasome to favor their function in antigen processing. Proteasomes are also ATP- and ubiquitin-dependent, as discussed in Section 6. 

Eukaryotic cells also have additional transport mechanisms. One of these is an ABC transporter (p. 417) known as the transporter associated with antigen processing (TAP). It carries small polypeptides generated by proteasomes from the cytosol into the ER for export and binding to MHC Class I molecules and subsequent presentation to the immune system (Fig. 31-15).540 602... 

As mentioned on p. 1854, an important function of proteasomes is formation of short antigenic peptides for use by the immune system.664 Inhibition of proteasome activity reduces or prevents antigen presentation (Chapter 31).665 666 In this immune surveillance system mature proteins of host cells are cut up and checked for self-identity. The checking also includes the rapidly degraded imperfect proteins and foreign proteins from invading organisms or viruses.667 6673... 

Apart from the immune system, there is little use for the degradation products released by the proteasome, and several peptidases exist which complete their conversion into free amino acids. One of them is tricorn peptidase, originally found in Thermoplasma cells, where it exists in the form of a giant icosahedral complex of approximately 15 MDa (Tamura et al., 1996 Walz et al., 1997). It has been shown in in vitro studies that tricorn in cooperation with an array of aminopeptidases converts oligopeptides of 8-12 residues efficiently into free amino acids (Tamura et al., 1998). Tricorn peptidase has been found in a number of archaeal and bacterial species, but it is not ubiquitous functional homologs are... 

Fig. 1. Schematic representation of the process of antigen presentation by MHC class I molecules. Endogenous proteins are degraded by the proteasome present in the cytoplasm and the nucleus. The resulting peptides are transported by TAP into the ER lumen. Most MHC class I molecules are bound to TAP in an antigen loading complex including tapasin as a bridging molecule. When loaded with peptide, MHC class I molecules are transported to the cell surface for presentation to the immune system...

Hypothyroidism, hyperthyroidism, and acromegaly can adversely affect respiratory muscle function (40). Proteolysis of myofibrillar proteins by the ubiquitin-proteasome proteolytic system is probably responsible for respiratory muscle catabolism and weakness of hyperthyroidism (40) This mechanism is implicated in the muscle wasting associated with acidosis, renal failure, cancer, diabetes, acquired immunity deficiency syndrome, trauma, and... 

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