Controlled destruction: AAA+ ATPases in protein degradation from bacteria to eukaryotes

Energy-dependent protein degradation is carried out by bipartite assemblies of conserved architecture. A chaperone ring comprising ATPase domains of the AAA+-type caps both ends of a hollow protease cylinder, thereby controlling access to the active sites. Hydrolysis of ATP is translated into a force that unfolds substrates and translocates them into the protease. Several recent advances reveal how the modular composition and cellular localization of these complexes contribute to their fine-tuned regulation. Crystal structures of the ubiquitin receptor Rpn13 as well as ClpS, the bacterial determinant of N-end rule degradation, in complex with their respective substrates demonstrate principles of substrate recognition by chaperone–proteases. Mechanistic studies show that polyubiquitin tags can act in trans to target nonubiquitinated substrates for degradation.