PA28αβ Reduces Size and Increases Hydrophilicity of 20S Immunoproteasome Peptide Products
| Autor: | Mary Raule, Gunnar Dittmar, Ami Navon, Fulvia Cerruti, Julia Kikuchi, Rebekka Migotti, Angela Bachi, Nadia Benaroudj, Paolo Cascio |
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| Rok vydání: | 2014 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Proteasome Endopeptidase Complex MHC class I antigen Clinical Biochemistry Allosteric regulation Peptide General Medicine Core Particle Biochemistry Cell biology Allosteric Regulation Proteasome chemistry Tandem Mass Spectrometry Catalytic Domain Immunoproteasomes Drug Discovery Molecular Medicine Efflux Particle Size Hydrophobic and Hydrophilic Interactions Molecular Biology |
| Zdroj: | Chemistry & Biology. 21:470-480 |
| ISSN: | 1074-5521 |
| Popis: | Summary The specific roles that immunoproteasome variants play in MHC class I antigen presentation are unknown at present. To investigate the biochemical properties of different immunoproteasome forms and unveil the molecular mechanisms of PA28 activity, we performed in vitro degradation of full-length proteins by 20S, 26S, and PA28αβ-20S immunoproteasomes and analyzed the spectrum of peptides released. Notably, PA28αβ-20S immunoproteasomes hydrolyze proteins at the same low rates as 20S alone, which is in line with PA28, neither stimulating nor preventing entry of unfolded polypeptides into the core particle. Most importantly, binding of PA28αβ to 20S greatly reduces the size of proteasomal products and favors the release of specific, more hydrophilic, longer peptides. Hence, PA28αβ may either allosterically modify proteasome active sites or act as a selective "smart" sieve that controls the efflux of products from the 20S proteolytic chamber. |
| Databáze: | OpenAIRE |
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