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

Abstract

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.