Figure 2.

General Post-Albers reaction scheme for P-type ATPases. A cytosolic ligand (yellow, transported ligand 1) is transported to the extracytosolic space, whereas an extracytosolic ligand (red, counter-transported ligand 2) is imported into the cytosol. Note that the number of ligands in each direction may vary between different P-type ATPase isoforms. In short, P-type ATPases switch between two major conformations E1, with ligand binding sites facing the cytosol, and E2, with ligand binding sites facing the extracytosolic side of the membrane. The induced fit of ligand 1 binding in E1 promotes phosphorylation by Mg⁺-ATP. In this E1~P state the ligand 1 becomes occluded. The rate-limiting E1~P to E2-P transition is accompanied by major conformational changes, reorienting the ligand-binding sites toward the extracytosolic space. This decreases the affinity of the binding site for ligand 1, whereas the affinity for ligand 2 is increased. As a result, ligand 1 is released into the extracytosolic space via an open exit pathway for ligand 1 and the counter-transported ligand 2 can enter the binding cavity. The resulting conformational changes lead to dephosphorylation of E2P and the released inorganic phosphate is expelled. The ligand 2 becomes occluded, whereupon the pump is reset to the E1 state, reducing the affinity for ligand 2. The pump can now start a new cycle.