biostudies-literatureSaratov GAMinistry of Science and Higher Education of the Russian Federation2091https://www.ebi.ac.uk/biostudies/studies/S-EPMC9917034biostudies-literatureUnknown24(3)Proteasomes exist in mammalian cells in multiple combinatorial variants due to the diverse regulatory particles and exchange of catalytic subunits. Here, using biotin carboxyl carrier domain of transcarboxylase from <i>Propionibacterium shermanii</i> fused with different proteasome subunits of catalytic and regulatory particles, we report comprehensive characterization of highly homogenous one-step purified human constitutive and immune 20S and 26S/30S proteasomes. Hydrolysis of a multiple sclerosis (MS) autoantigen, myelin basic protein (MBP), by engineered human proteasomes with different catalytic phenotypes, revealed that peptides which may be directly loaded on the HLA class I molecules are produced mainly by immunoproteasomes. We detected at least five MBP immunodominant core regionsInternational journal of molecular sciencesMyelin Basic Protein Fragmentation by Engineered Human Proteasomes with Different Catalytic Phenotypes Revealed Direct Peptide Ligands of MS-Associated and Protective HLA Class I Molecules.PMC9917034075-15-2020-795RF-190220X002713.1902.21.0027Konevega ALBelogurov AAKudriaeva AASaratov GAChen GBaymukhametov TNZiganshin RHVladimirov VINovoselov ALfalseMyelin Basic Protein Fragmentation by Engineered Human Proteasomes with Different Catalytic Phenotypes Revealed Direct Peptide Ligands of MS-Associated and Protective HLA Class I Molecules.Proteasomes exist in mammalian cells in multiple combinatorial variants due to the diverse regulatory particles and exchange of catalytic subunits. Here, using biotin carboxyl carrier domain of transcarboxylase from <i>Propionibacterium shermanii</i> fused with different proteasome subunits of catalytic and regulatory particles, we report comprehensive characterization of highly homogenous one-step purified human constitutive and immune 20S and 26S/30S proteasomes. Hydrolysis of a multiple sclerosis (MS) autoantigen, myelin basic protein (MBP), by engineered human proteasomes with different catalytic phenotypes, revealed that peptides which may be directly loaded on the HLA class I molecules are produced mainly by immunoproteasomes. We detected at least five MBP immunodominant core regions2023-01-01T00:00:00Z2023 Jan2026-04-08T13:58:50.196Z2025-04-06T00:50:59.472ZS-EPMC99170343676841310.3390/ijms24032091