Project Details
Projekt
Mutationsanalyse der Proteasomenfunktion (Mutational analysis of proteasome function)
Applicant
Dr. Wolfgang Heinemeyer
Subject Area
Biochemistry
Term
from 1998 to 2004
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5111426
Mutant forms of the Saccharomyces cerevisiae proteasome served to elucidate several new aspects concerning the particle's maturation and the mechanism of substrate degradation. Collaborations with the research groups of Prof. Huber, Munich and Prof. Rammensee, Tübingen, which we supplied with existing and newly created mutant material contributed to the successful outcome of most of the projects presented in our first application. We plan to continue attacking mechanistic problems of 20S proteasome maturation, its proteolytic action and its regulation by a combination of yeast molecular genetics and structural/chemical analytic tools. In one project we will analyze the role of a-type subunit phosphorylation for regulation of proteasome activity, assembly of the 26S proteasome or cellular distribution of the complex. In a second project we will either give new insights into the role of the b6 subunit propeptide during particle maturation or reveal a novel function of the b6 propeptide piece that stays attached in the matured particle. In a third project we will deal with the reactivation of inactive b-type subunits and with the exchange of subunit specificities using a domain swapping approach. By this we would like to answer the yet unsolved question of the reduction of active site number in the eukaryotic proteasome as compared to the archaebacterial proteasome and to uncover spatial requirements for the cooperative action of the catalytic sites. In a fourth project the different requirements of the yeast and mammalian proteasome for processing of the NF-KB precursor p105 will be analysed.
DFG Programme
Priority Programmes
