PA28 SUBUNITS OF THE MOUSE PROTEASOME - PRIMARY STRUCTURES AND CHROMOSOMAL LOCALIZATION OF THE GENES

The 20S proteasome is a multi-subunit protease responsible for the pro duction of peptides presented by major histocompatibility complex (MHC ) class I molecules. Recent evidence indicates that an interferon-gamm a (IFN-gamma)-inducible PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the p roteasome. In the present study, we determined the primary structures of the mouse PA28 alpha- and beta-subunits. The deduced amino acid seq uences of the alpha- and beta-subunits were 49% identical. We also det ermined the primary structure of the mouse PA28 gamma-subunit (Ki anti gen), a protein of unknown function structurally related to the alpha- and beta-subunits. The amino acid sequence identity of the gamma-subu nit to the alpha- and beta-subunits was 40% and 32%, respectively. Int erspecific backcross mapping showed that the mouse genes coding for th e alpha- and beta-subunits (designated Pslne1 and Psme2, respectively) are tightly linked and map close to the Atp5g1 locus on chromosome 14 . Thus, unlike the LMP2 and LMP7 subunits, the IFN-gamma-inducible sub units of PA28 are encoded outside the MHC. The gene coding for the gam ma-subunit (designated Psme3) was mapped to the vicinity of the Brca1 locus on chromosome 11. A computer search of the DNA databases identif ied a gamma-subunit-like protein in ticks and Caenorhabditis elegans, the organisms with no adaptive immune system. It appears that the IFN- gamma-inducible alpha- and beta-subunits emerged by gene duplication f rom a gamma-subunit-like precursor.