Figure 4. Sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA) transporting cycle.

E1 indicates SERCA conformation characterized by a high affinity for Ca²⁺. E1-E2 represents a transient high energy state. E2 represents SERCA conformation characterized by a low affinity for Ca²⁺. Two cytosolic Ca²⁺ ions bind to SERCA in E1 conformation. ATP tethers to the nucleotide (N) domain and phosphorylates the (P) domain. The phosphorylated (P) domain interacts with the (A) domain resulting in two sequential conformational changes (E1-E2, and E2). SERCA in E2 conformation releases Ca²⁺ into the SR lumen. Pi, inorganic phosphate; ADP, adenosine diphosphate; H⁺, proton.