While significant advances have been made over the past decade in elucidating the structure and enzymatic mechanism of the 20S proteasome, the 26S complex has remained structurally ill-defined. In the 26S proteasome 19S 'cap' complexes associate with either one or both ends of the barrel-shaped 20S core complex. These regulatory complexes which comprise at least 16 different subunits, bind (ubiquitinated) target proteins and present them to the 20S proteolytic core in an unfolded form. It is our goal to determine the molecular architecture of this regulatory complex, isolated and associated with a 20S complex, and to monitor the fate of substrates, mainly by time-resolved 3D-electron microscopy. Moreover, we will study simpler prokaryotic precursors of this regulatory complex which contain, as it appears, only ATPase-subunits, belonging to the AAA-ATPase family.
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