The regulation of proteolysis by the proteasome. (a) The three-dimensional structure of the 26S proteasome is highly conserved in all eukaryotes. The two subassemblies are the 20S core particle (light and dark brown) and the 19S regulatory particle (gray), one at each end of the core. (b) The core particle consists of four rings arranged in a barrel-like structure. Each inner ring has seven different β subunits (dark brown), three of which have protease activity; each outer ring has seven different α subunits (light brown). At each end of the core, the 19S regulatory particle forms a cap (composed of base and lid segments). The regulatory particles are thought to unfold ubiquitinated proteins and translocate them into the core particle for destruction.