Immunoproteasome

Structurally, immunoproteasome is a cylindrical protein complex composed of a catalytic 20S subunit and a 19S regulatory subunit. The catalytic subunit consists of four outer alpha rings and four inner beta rings. The LMP2 protein is composed of 20 amino acids, MECL-1 of 39 amino acids and LMP7 occurs in isoform and therefore can have either 72 or 68 amino acids. == Function ==

The function of the immunoproteasome is primarily to specifically cleave proteins into shorter peptides, which can then be displayed on the cell surface together with the MHC I complex. The MHC I complex with bound peptide is then recognized primarily by cytotoxic T cells. In order to expose a peptide on the cell surface, the ubiquitin-labeled protein, specifically cleaved into peptides by immunoproteasome, must first be transferred to the endoplasmic reticulum using TAP1 and TAP2 transporters and chaperones. In the endoplasmic reticulum, the peptide is then bound to an MHC I molecule. The aforementioned LMP2 and LMP7 subunits are encoded by the PSMB9 (LMP2) and PSMB8 (LMP7) genes, which are found in the MHC II gene cluster of the TAP-1 and TAP-2 genes. The LMP2 subunit has the function of chymotrypsin, which means that it cleaves bonds after hydrophobic substances and this prepares peptides with hydrophobic C anchors for the MHC I complex. While LMP7 and MECL-1 subunits form the same as the standard proteasome subunits, i.e. trypsin and chymotrypsin activity == Diseases associated with immunoproteasome ==

The ability to display peptides on the cell surface is essential for the recognition of cell status by immune cells. Its proper function is therefore essential and when it is disrupted, a disease occurs. Some examples where the effect of immunoproteasome on pathology has been confirmed are given below: Mutations in the PSMB8 gene, which encodes the LMP7 subunit, are involved in a variety of diseases and autoinflammatory disorders, the symptoms of which include skin rash, erythema, spiking fever and lipodystrophy, which are presented since early childhood. These also include Nakajo-Nishimura syndrome, a Japanese autoinflammatory syndrom with lipodystrophy syndrome (JASL) or chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature. This list of syndromes is collectively called proteasome-associated autoinflammatory syndrome. == References ==