Structural bases of physiological functions and roles of the vacuolar H+-ATPase

Vacuolar-type H+-ATPases (V-ATPases) is a large multi-protein complex containing at least 14 different subunits, in which subunits A, B, C, D, E, F, G, and H compose the peripheral 500-kDa V1 responsible for ATP hydrolysis, and subunits a, c, c′, c″, and d assembly the 250-kDa membrane-integral V0 harboring the rotary mechanism to transport protons across the membrane. The assembly of V-ATPases requires the presence of all V1 and V0 subunits, in which the V1 must be completely assembled prior to association with the V0, accordingly the V0 failing to assemble cannot provide a membrane anchor for the V1, thereby prohibiting membrane association of the V-ATPase subunits. The V-ATPase mediates acidification of intracellular compartments and regulates diverse critical physiological processes of cell for functions of its numerous functional subunits. The core catalytic mechanism of the V-ATPase is a rotational catalytic mechanism. The V-ATPase holoenzyme activity is regulated by the reversible assembly/disassembly of the V1 and V0, the targeting and recycling of V-ATPase-containing vesicles to and from the plasma membrane, the coupling ratio between ATP hydrolysis and proton pumping, ATP, Ca2+, and its inhibitors and activators.