Assembly and regulation of the yeast vacuolar H+-ATPase

The yeast vacuolar proton-translocating ATPase (V-ATPase) is an excellent model for V-ATPases in all eukaryotic cells. Activity of the yeast V-ATPase is reversibly down-regulated by disassembly of the peripheral (V-1) sector, which contains the ATP-binding sites, from the membrane (V-0) sector, which contains the proton pore. A similar regulatory mechanism has been found in Manduca sexta and is believed to operate in other eukaryotes. We are interested in the mechanism of reversible disassembly and its implications for V-ATPase structure. In this review, we focus on (1) characterization of the yeast V-ATPase stalk subunits, which form the interface between V-1 and V-0, (2) potential mechanisms of silencing ATP hydrolytic activity in disassembled V-1 sectors, and (3) the structure and function of RAVE, a recently discovered complex that regulates V-ATPase assembly.