Rotary mechanism of V/A-ATPases-how is ATP hydrolysis converted into a mechanical step rotation in rotary ATPases?

V/A-ATPase is a rotary molecular motor protein that produces ATP through the rotation of its central rotor. The soluble part of this protein, the V domain, rotates upon ATP hydrolysis. However, the mechanism by which ATP hydrolysis in the V domain couples with the mechanical rotation of the rotor is still unclear. Cryo-EM snapshot analysis of V/A-ATPase indicated that three independent and simultaneous catalytic events occurred at the three catalytic dimers (AB , AB , and AB ), leading to a 120° rotation of the central rotor. Besides the closing motion caused by ATP bound to AB , the hydrolysis of ATP bound to AB drives the 120° step. Our recent time-resolved cryo-EM snapshot analysis provides further evidence for this model. This review aimed to provide a comprehensive overview of the structure and function of V/A-ATPase from a thermophilic bacterium, one of the most well-studied rotary ATPases to date.