¨r Biochemie Am Klopferspitz 18a the chaperonins and have been referred to as "reverse chaperones" or "unfoldases" (Lupas et al., 1993). Since D-82152 Martinsried Germany their action requires the hydrolysis of ATP, protein degradation becomes energy-dependent, although the hydrolysis of the polypeptide chain itself is an exergonic Controlling Proteolysis process. through CompartmentalizationSelf-compartmentalizing proteases are common in all Protein degradation is a necessity for many reasons: three domains of life: archaea, bacteria, and eukarya. Homeostasis must be maintained while cellular struc-This bears testimony to an old evolutionary principle. In tures are continually rebuilt, in particular during developfact, contrary to organelles such as the lysosome, selfment or in response to external stimuli. Proteins miscompartmentalizing molecular devices offer far greater folded as a consequence of mutations or ensuing from flexibility: when equipped with the appropriate localizaheat or oxidative stress must be scavenged because tion signals, they can be deployed to different cellular they are prone to aggregation. Beyond these more munlocations in the cytosol or in the nucleus, wherever their dane "housekeeping" functions, protein degradation action is needed. The advances made in recent years provides a means to terminate the lifespan of many in understanding the structure of the proteasome and its regulatory proteins at distinct times; amongst them are mechanism of action has helped to shape the concept of cyclins, transcription factors, and components of signal self-compartmentalization, and the proteasome became transduction pathways (for reviews, see Coux et al., the paradigm of this form of regulation. 1996; Hilt and Wolf, 1996;Varshavsky, 1997). Moreover, the immune system relies on the availability of immuno-The 20S Proteasome: Core of the competent peptides generated by the degradation of Proteolytic Machinery foreign antigens (for reviews, see Goldberg et al., 1995; 20S Proteasomes Are Found in All Three Heemels and Ploegh, 1995).Domains of Life However, since protein degradation is also a hazard,The first description of a "cylinder-shaped" complex it must be subject to spatial and temporal control in with proteasome-like features dates back to the late order to prevent the destruction of proteins not destined sixties. The plethora of names given to it subsequently for degradation. A basic stratagem in controlling protein is a reflection of the problems that were encountered degradation is compartmentalization, that is, the conover a period of two decades in trying to define its finement of the proteolytic action to sites that can only biochemical properties and cellular functions. Enzymobe accessed by proteins displaying some sort of degralogical studies revealed an array of distinct proteolytic dation signal. Such a compartment can be an organelle activities and led to a consensus name, "multicatalytic delimited by a membrane, as in the case of the lysosome.proteinase" (Dahlmann et al., 1988). ...
