Figure 2.

E1-E2 Ca transport scheme via which SERCA2a transports Ca into the sarcoplasmic reticulum (SR) lumen. Stage 1: In the E1 conformation, the high-affinity Ca²⁺ binding sites are accessible by the cytosol. Two protons leave the pump as ATP binds to allow access to the cytosol. Stage 2: 2 Ca²⁺ ions bind with high affinity. Stage 3: Bound ATP is used to phosphorylate Asp³⁵¹, causing a conformational change which occludes Ca²⁺. At this point, the pump is in the high-energy unstable phosphointermediate condition. Stage 4: A further conformational change brings about the E2 form of SERCA2a where the SR lumen is accessible to Ca²⁺. Ca²⁺ ions are released because of a lower affinity in the E2 state. Stage 5: Protons replace Ca²⁺. Stage 6: Asp³⁵¹ is dephosphorylated, bringing the pump into a low-energy intermediate form, which is unstable and returns to the E1 state.