要旨
Because of the potential damage to the cell, intracellular protein degradation is one of the most tightly regulated processes in living systems. As a consequence, all protein breakdown in the cell is energy dependent, even though proteolysis is fundamentally exergonic. The basic regulatory strategy has been the confinement of proteolytic active sites to internal compartments with tightly controlled access. In eukaryotes this has eventually led to the evolution of a dedicated organelle, the lysosome, in which the primary energy-dependent step is the translocation of substrates across the membrane. The oldest solution, however (which still handles the bulk of intracellular proteolysis even in eukaryotes) is a set of proteases that form barrel-shaped complexes through self-association, enclosing a central proteolytic cavity (Lupas et al. 1997b). Access to this cavity is provided by polar pores guarded by ring-shaped ATPases, which unfold and translocate substrate proteins in an energy-dependent manner. Prokaryotes contain several such proteases, including Lon, ClpAP, ClpXP, FtsH, and proteasomes, but the only one present outside of organelles in eukaryotes is the proteasome.
