Detailseite
Projekt
Spezifität und Mechanismus des eukaryotischen 20S/26S Proteasoms (Specificity and mechanism of the eukaryotic 20S/26S proteasome)
Antragsteller
Professor Dr. Hansjörg Schild
Fachliche Zuordnung
Biochemie
Förderung
Förderung von 1998 bis 2007
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5109996
Immunologists are interested in proteasomes because their cleavage specificities influence directly the generation of CTLepitopes. So far, proteasomal specificities have been investigated using fluorogenic peptides or synthetic peptides containing CTL epitopes as substrates. Based on amino acids at the P1 position, chymotrypsin-like, trypsin-like and Peptidy-GlutamylPeptid-Hydrolase (PGPH) activities have been described. These experiments also revealed that additional amino acids, besides those at the P1 position, influence the cleavage site selection of 20S proteasomes. This became even more obvious when peptide fragments generated from yeast 20S proteasomes after incubation with substrate proteins were analyzed allowing the identification of rules that govern the specificities of individual bsubunits. We have now planned to identify these rules also in mammalian 20S and 26S proteasomes with a special interest in the influence of the interferon-inducible b-subunits LMP2, LMP7 and MECL1 on the cleavage specificities. This information will improve the prediction of new CTL-epitopes and the development of b-subunit specific proteasome inhibitors.
DFG-Verfahren
Schwerpunktprogramme
Beteiligte Person
Professor Dr. Hans-Georg Rammensee
