Proteasomes and their kin: Proteases in the machine age

'Chambered proteases', including the eukaryotic 26S proteasome, use the energy of ATP to drive the unfolding and translocation of a polypeptide substrate into a chamber of sequestered proteolytic active sites. These proteases have diverse functions and are found in all three kingdoms of life. Understanding chambered proteases requires answers to two questions - how do these remarkable machines select the correct target proteins and how do they bring about the processive degradation of these molecules?