AAA Proteins: Lords of the Ring

AAA ATPases (those associated with various cellular activities) 1 play important roles in numerous cellular activities including proteolysis, protein folding, membrane trafficking, cytoskeletal regulation, organelle biogenesis, DNA replication, and intracellular motility. Recent structural and enzymatic studies are providing clues into the properties of the conserved AAA domain that defines this large protein superfamily. In many cases, AAA domains assemble into hexamic rings that are likely to change their shape during the ATPase cycle. This nucleotide-dependent conformational switch may apply tension to bound proteins and thereby allow AAA proteins to unfold polypeptides, dissociate protein–protein interactions, or generate unidirectional motion along a track. Thus, AAA proteins may represent a broad class of mechanoenzymes that have evolved unique ways of using a fundamentally similar conformational change in many different biological settings.