TY  - JOUR
A1  - Kuckelkorn, Ulrike
A1  - Stübler, Sabine
A1  - Textoris-Taube, Kathrin
A1  - Kilian, Christiane
A1  - Niewienda, Agathe
A1  - Henklein, Petra
A1  - Janek, Katharina
A1  - Stumpf, Michael P. H.
A1  - Mishto, Michele
A1  - Liepe, Juliane
T1  - Proteolytic dynamics of human 20S thymoproteasome
JF  - The journal of biological chemistry
N2  - 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.
KW  - proteasome
KW  - protein degradation
KW  - antigen processing
KW  - computational biology
KW  - bioinformatics
KW  - thymoproteasome
KW  - thymus
KW  - proteolysis
Y1  - 2019
U6  - https://doi.org/10.1074/jbc.RA118.007347
SN  - 1083-351X
VL  - 294
IS  - 19
SP  - 7740
EP  - 7754
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  -