Ca²⁺ ATPase
Eukaryotic cells maintain a low concentration of free Ca²⁺ in the cytosol (10-7 M) whereas the extracellular concentration is very high on the opposite face (10-3 M). Henceforth, a small influx of Ca²⁺ significantly increases the concentration of free Ca²⁺ in the cytosol and the flow of Ca²⁺ down its steep concentration gradient in response to the extracellular signals is one of the means of transmitting these signals rapidly across the plasma membrane. Hence cells maintain a steep Ca²⁺ gradient across the plasma membrane. The Ca²⁺ ATPases are commonly found in muscle cells and neurons. The skeletal muscle have specialized structure of large intracellular Ca²⁺ stores called sarcoendoplasmic recticulum which controls Ca²⁺ uptake and release throughout the cell volume. These are mainly responsible for Ca²⁺ extrusion from cytosol in muscle cells which is required to stop muscle contraction and to initiate relaxation.
Ca²⁺ transporters are the common example of P-type transport ATPase. It is also known as Ca²⁺ pump or Ca²⁺ ATPase or SERCA pump (Sacroendoplasmic recticulum Ca²⁺ ATPase). These transporters actively pump Ca²⁺ out of the cell and helps in maintaining the gradient. The structure of Ca²⁺ pump has an asymmetrical arrangement of transmembrane and cytosolic domains that undergo movements during Ca²⁺ transport. It contains 10 tranmembrane α-helices and two cytoplasmic loops between the transmembrane α-helices. The transmembrane α-helices form Ca²⁺ binding site which binds two Ca²⁺ ions from cytosol. And the two cytoplasmic loops form three separate domains: nucleotide binding domains that binds ATP, actuator domain that contains catalytic phoshorylation site and P domain which is important for transmission of conformational changes between cytosolic and transmembrane domains. In unphosphorylated state, the two helices are disturbed and form a cavity for binding of two Ca²⁺ ions from the cytosolic side of the membrane. ATP also binds to a binding site on the same side of the membrane and the subsequent transfer of the terminal phosphate group of ATP to an aspartic acid of an adjacent domain lead to a drastic rearrangement of the transmembrane helices. This rearrangement disturbs the Ca²⁺ binding site and releases Ca²⁺ ions on the other side of the membrane that is into the lumen of SR. With respect to figure 5 and 6, the mechanism of the Ca²⁺ ATPase in the SR membrane can be understood clearly through following steps:

1. The protein in E1 conformation has two high affinity binding sites for Ca²⁺ ions accessible from the cytosolic side and ATP binds to a side on cytosolic surface.
   
2. In the presence of Mg²⁺, the bound form of ATP is hydrolyzed to ADP and phosphate. Later the liberated phosphate is transferred to a specific aspartate residue in the protein, forming the high-energy acyl phosphate bond denoted by E1 ~ P.
   
3. Then the protein undergoes a conformational change and generates E2, which has two low-affinity Ca²⁺ binding sites accessible to the SR lumen.
   
4. The free energy of E1 ~ P is greater than E2-P, and this reduction in free energy leads to the E1 → E2 conformational change. Simultaneously, the Ca²⁺ ions also dissociate from the low-affinity sites to enter the SR lumen, following which the aspartyl-phosphate bond is hydrolyzed.
   
5.  Dephosphorylation then again leads to the E2 → E1 conformational change, and E1 is ready to transport two more Ca²⁺ ions.