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Proteolytic dynamics of human 20S thymoproteasome
- An efficient immunosurveillance of CD8(+) T cells in the periphery depends on positive/negative selection of thymocytes and thus on the dynamics of antigen degradation and epitope production by thymoproteasome and immunoproteasome in the thymus. Although studies in mouse systems have shown how thymoproteasome activity differs from that of immunoproteasome and strongly impacts the T cell repertoire, the proteolytic dynamics and the regulation of human thymoproteasome are unknown. By combining biochemical and computational modeling approaches, we show here that human 20S thymoproteasome and immunoproteasome differ not only in the proteolytic activity of the catalytic sites but also in the peptide transport. These differences impinge upon the quantity of peptide products rather than where the substrates are cleaved. The comparison of the two human 20S proteasome isoforms depicts different processing of antigens that are associated to tumors and autoimmune diseases.
Author details: | Ulrike Kuckelkorn, Sabine StüblerORCiDGND, Kathrin Textoris-TaubeGND, Christiane Kilian, Agathe Niewienda, Petra Henklein, Katharina Janek, Michael P. H. Stumpf, Michele MishtoORCiD, Juliane LiepeORCiD |
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DOI: | https://doi.org/10.1074/jbc.RA118.007347 |
ISSN: | 1083-351X |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30914481 |
Title of parent work (English): | The journal of biological chemistry |
Publisher: | American Society for Biochemistry and Molecular Biology |
Place of publishing: | Bethesda |
Publication type: | Article |
Language: | English |
Date of first publication: | 2019/02/26 |
Publication year: | 2019 |
Release date: | 2021/02/11 |
Tag: | antigen processing; bioinformatics; computational biology; proteasome; protein degradation; proteolysis; thymoproteasome; thymus |
Volume: | 294 |
Issue: | 19 |
Number of pages: | 15 |
First page: | 7740 |
Last Page: | 7754 |
Funding institution: | London; Berlin Institute of Health [CRG1-TP1] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Mathematik |
DDC classification: | 5 Naturwissenschaften und Mathematik / 51 Mathematik / 510 Mathematik |
Peer review: | Referiert |
Publishing method: | Open Access / Green Open-Access |
License (German): | CC-BY - Namensnennung 4.0 International |