Model of the subunit architecture of eukaryotic vacuolar ATPase.

(A) V₁-ATPase (top) and membrane bound V_o proton channel (bottom) are linked by three peripheral stalks (EG1, EG2, EG3) that connect the top of the V₁ to subunits C, H, and the N-terminal domain of the membrane integral subunit a (a_NT). Subunits C, H and a_NT are two domain proteins with C_head and C_foot, H_NT and H_CT, a_NT(proximal) and a_NT(distal) domains, respectively. (B) During enzyme regulation by reversible dissociation, V₁-ATPase is released from the membrane bound V_o and the activity of both resulting complexes is silenced. To enable enzyme disassembly, protein-protein interactions involving subunits EG, C, H, DF, d and a_NT have to be broken.