Vacuolar-type ATPases (V-ATPases) are membrane-embedded proton pumps that acidify intracellular compartments in almost all eukaryotic cells. Homologous with ATP synthases, these multisubunit enzymes consist of a soluble catalytic V(1) subcomplex and a membrane-embedded proton-translocating V(O) subcomplex. The V(1) and V(O) subcomplexes can undergo reversible dissociation to regulate proton pumping, with reassociation of V(1) and V(O) requiring the protein complex known as RAVE (regulator of the ATPase of vacuoles and endosomes). In the yeast Saccharomyces cerevisiae, RAVE consists of subunits Rav1p, Rav2p, and Skp1p. We used electron cryomicroscopy (cryo-EM) to determine a structure of yeast RAVE bound to V(1). In the structure, RAVE is an L-shaped complex with Rav2p pointing toward the membrane and Skp1p distant from both the membrane and V(1). Only Rav1p interacts with V(1), binding to a region of subunit A not found in the corresponding ATP synthase subunit. When bound to RAVE, V(1) is in a rotational state suitable for binding the free V(O) complex, but in the structure, it is partially disrupted, missing five of its 16 subunits. Other than these missing subunits and the conformation of the inhibitory subunit H, the V(1) complex with RAVE appears poised for reassembly with V(O).

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Wang H, Tarsio M, Kane PM, Rubinstein JL

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