Composition and assembly of the yeast vacuolar H+-ATPase complex

The proton-translocating ATPase (H+-ATPase) found on the membrane of the ye ast vacuole is the best characterized member of the V-type ATPase family. B iochemical and genetic screens have led to the identification of 14 genes, the majority designated VMA (for vacuolar membrane ATPase) encoding subunit s of the enzyme complex. At least eight genes encode for proteins comprisin g the peripherally associated catalytic V-1 subcomplex, and six genes code for proteins forming the proton-translocating membrane Yr, subcomplex. Seve ral additional genes have been identified that encode proteins that are not part of the final V-ATPase complex yet are required for its assembly. Thes e non-subunit Vma proteins function as dedicated V-ATPase assembly factors since their absence appears to inhibit assembly of the V-ATPase only. The a ssembly factors designated Vma12p, Vma21p and Vma22p have been localized to the membrane of the endoplasmic reticulum and aid the association of newly synthesized V-ATPase subunits translocated into the endoplasmic reticulum membrane. Two of these proteins, Vma12p and Vma22p, function together in an assembly complex that interacts directly with nascent V-ATPase subunits.