Marching to the beat of the ring: polypeptide translocation by AAA+ proteases

• ATP-dependent proteases contain a hexameric unfoldase for protein translocation.
• Rigidity within unfoldase ring leads to preferred order of ATP hydrolysis events.
• Subunits in the hexamer are coordinated in their conformational changes.

ATP-dependent proteases exist in all cells and are crucial regulators of the proteome. These machines consist of a hexameric, ring-shaped motor responsible for engaging, unfolding, and translocating protein substrates into an associated peptidase for degradation. Here, we discuss recent work that has established how the six motor subunits coordinate their ATP-hydrolysis and translocation activities. The closed topology of the ring and the rigidity of subunit/subunit interfaces cause conformational changes within a single subunit to drive motions in other subunits of the hexamer. This structural effect generates allostery between the ATP-binding sites, leading to a preferred order of binding and hydrolysis events among the motor subunits as well as a unique biphasic mechanism of translocation.