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 V-1 responsible for ATP hydrolysis, and subunits a, c, c', c '', and d assembly the 250-kDa membrane-integral V-0 harboring the rotary mechanism to transport protons across the membrane. The assembly of V-ATPases requires the presence of all V-1 and V-0 subunits, in which the V-1 must be completely assembled prior to association with the V-0, accordingly the V-0 failing to assemble cannot provide a membrane anchor for the V-1, 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 V-1 and V-0, 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. (C) 2011 Elsevier Inc. All rights reserved.