THE PROTEASOME - A MACROMOLECULAR ASSEMBLY DESIGNED TO CONFINE PROTEOLYSIS TO A NANOCOMPARTMENT

Significant progress has been made over the past few years in elucidat ing the structural principles and the enzymatic mechanism of the 20S p roteasome. As a result, the proteasome has become the prototype of a n ew family of enzymes, the Ntn hydrolases, as well as a paradigm for ma cromolecular assemblies that confine their proteolytic activity to an inner nanocompartment. Since access to this nanocompartment is restric ted to unfolded substrate polypeptides, the 20S proteasome must be fun ctionally linked to a substrate recognition and unfolding machinery. I n eukaryotes this is provided by the 19S 'cap' complex, which associat es with the 20S core to form the 26S proteasome, a protease capable of degrading ubiquitinated proteins in an ATP-dependent manner.