Proteasomes: unfoldase-assisted protein degradation machines

Proteasomes are the principal molecular machines for the regulated degradation of intracellular proteins. These self- compartmentalized macromolecular assemblies selectively degrade misfolded, mistranslated, damaged or otherwise unwanted proteins, and play a pivotal role in the maintenance of cellular proteostasis, in stress response, and numerous other processes of vital importance. Whereas the molecular architecture of the proteasome core particle (CP) is universally conserved, the unfoldase modules vary in overall structure, subunit complexity, and regulatory principles. Proteasomal unfoldases are AAA+ ATPases (ATPases associated with a variety of cellular activities) that unfold protein substrates, and -translocate them into the CP for degradation. In this review, we summarize the current state of knowledge about proteasome - unfoldase systems in bacteria, archaea, and eukaryotes, the three domains of life.