The function of chaperones and proteases in protein quality control and intracellular protein degradation

Abstract

Abstract During the last few years we have witnessed a major revolution in our understanding of the importance and the mechanism of intracellular protein degradation. We have come to appreciate that highly selective protein degradation occurs in all organisms and is a component of many essential regulatory pathways. We have also learned that protein degradation plays an important part in maintaining protein quality control within the cell. Most excitingly, we now have a grasp of the basic mechanism of ATP-dependent protein degradation and have begun to develop an understanding of how cells protect their proteins from inadvertent destruction while assuring that appropriate proteins are efficiently targeted for degradation. Studies of the structure and mechanism of the ATP-dependent proteases responsible for the majority of intracellular protein degradation have revealed unanticipated parallels between the proteolytic machinery of cells and the molecular chaperone systems responsible for the folding of cellular proteins and the assembly or disassembly of macromolecular complexes. This progress has led to a unified model of protein degradation and protein quality control, in which protein surveillance and structural remodelling mediated by chaperone systems and the chaperone components of ATPdependent proteases serve as the keystone.