Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes.
Juliane Liepe, Hermann-Georg Holzhütter, Elena Bellavista, Peter M Kloetzel, Michael PH Stumpf, Michele Mishto
Elife | Published : 2015
Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of interactions between substrates and products and the proteolytic and regulatory sites; the locations of these sites and the interactions between them are predi..View full abstract
Awarded by National Centre for the Replacement, Refinement and Reduction of Animals in Research
Awarded by Biotechnology and Biological Sciences Research Council