Structure, function and regulation of the coated vesicle V-ATPase

The coated vesicle V-ATPase plays an important role in both receptor-mediated endocytosis and intracellular membrane traffic by providing the acidic environment required for ligand-receptor dissociation and receptor recycling. The coated vesicle V-ATPase is a macromolecular complex of relative molecular mass 750000 composed of nine subunits arranged in two structural domains. The peripheral V₁ domain, which has a relative molecular mass of 500000, has the subunit structure 73₃58₃40₁34₁33₁ and possesses all the nucleotide binding sites of the V-ATPase. The integral V_o domain of relative molecular mass 250000 has a subunit composition of 100₁38₁19₁17₆ and possesses the pathway for proton conduction across the membrane. Reassembly studies have allowed us to probe the role of specific subunits in the V-ATPase complex while chemical labeling studies have allowed us to identify specific residues which play a critical role in catalysis. From both structural analysis and sequence homology, the vacuolar-type H⁺-ATPases resemble the F-type H⁺-ATPases. Unlike the F₁ and F₀ domains of the F-type ATPases, however, the V₁ and V_o domains do not appear to function independently. The possible relevance of these observations to the regulation of vacuolar acidification is discussed.