The proteasome is a multisubunit protease complex responsible for the generation of peptides presented by MHC class I molecules. The catalytic core of this complex, known as the 20S proteasome, is a cylinder-shaped particle made up of four layers of rings. Each ring is composed of seven subunits, with the α subunits forming the two outer rings and the β subunits the two inner rings. The catalytic center of the 20S proteasome resides on the N-terminal threonine residue of the β subunit. In eukaryotes, 14 (7 α and 7 β) structurally distinct subunits are assembled into a single complex. The center of the α ring is almost closed, preventing random penetration of proteins into the interior of the cylinder. Thus, the proteasome is a typical example of a self-compartmentalizing protease.
Interferon-γ (IFN-γ) induces the formation of a specialized type of 20S proteasomes, designated immunoproteasomes. When cells are stimulated with IFN-γ, three IFN-γ-inducible β subunits, known as PSMB9/LMP2, PSMB8/LMP7 and PSMB10/MECL1, are incorporated into the 20S proteasome by displacing the homologous house-keeping beta subunits. Immunoproteasomes containing the IFN-γ inducible β subunits produce class I-binding peptides more efficiently than those containing only housekeeping β subunits.
Besides the formation of immunoproteasomes. IFN-γ induces the assembly of a regulatory unit that binds to the α rings of the 20S proteasome. This regulatory unit, the proteasome activator PA28 (or REG), is a ring-shaped heteropolymer made up of two related subunits, PA28 α and PA28 β. Although PA28 is a heteroheptamer made up of 7 subunits of Mr 28,000 (α3β4 or a mixture of α3β4 and α4β3). Enhanced expression of the PA28 α subunit in virus-infected fibroblasts results in more efficient presentation of viral peptides to cytotoxic T cells. Mice lacking the PA28 β subunit show impaired cytotoxic T cell responses, suggesting a critical role for PA28 in MHC class I-mediated antigen presentation.
The mouse genes, Psme1 and Psme2, coding for the PA28 α and β subunits, respectively, are located ~6 kb apart with their 3' ends pointing toward each other on bands C2-D1 of Chromosome 14 .