Since cellular structures are rebuilt continually, protein degradation is essential for the maintenance of homeostasis. Misfolded proteins ensuing from genetic defects or environmental stress, are prone to aggregation; chaperones and proteases cooperate in minimizing such unproductive interactions. Last, but not least, protein degradation serves to terminate the lifespan of many regulatory proteins at distinct times and thus features as a key regulatory element itself. Proteins destined for degradation must be recognized and selected within the crowded environment of the cell. The stratagem of self-compartmentalization is key to controlling cellular proteolysis (1).

In recent years, a number of multisubunit proteolytic complexes have been described which possess large internal cavities or nano-compartments. This allows them to confine the proteolytic action to their interior; access to these inner compartments is usually restricted to the unfolded proteins. This, in turn, makes it necessary for these proteases to interact - either in a transient or in a permanent manner