Calcium Pump - How The Calcium Pump Works

How The Calcium Pump Works

Classical Theory of active transport for P-type ATPases

E1 → (2H+ out, 2Ca2+ in)→ E1⋅2Ca2+ → E1⋅ ATP
E2 E1⋅ADP
↑(Pi out) ↓(ADP out)
E2⋅Pi ← E2P ←(2H+ in, 2Ca2+ out) ← E1P

Data from crystallography studies by Chikashi Toyoshima applied to the above cycle

E1 - high affinity for Ca2+, 2 Ca2+ bound, 2 H+ counter ions released
E1⋅2Ca2+ - cytoplasmic gate open, free Ca2+ ion exchange occurs between bound ions and those in cytoplasm, closed configuration of N, P, A domains broken, exposing catalytic site
E1⋅ ATP - ATP binds and links N to P, P bends, N contacts A, A causes M1 helix to pull up, closes cytoplasmic gate, bound Ca2+ occluded in transmembrane
E1⋅ADP - Phosphoryl transfer, ADP dissociates
E1P - A rotates, transmembrane helices rearrange, binding sites destroyed, lumenal gate opened, bound Ca2+ released
E2P - open ion pathway to lumen, Ca2+ to lumen
E2⋅Pi - A catalyzes release of the Pi, P unbends, transmembrane helices rearranged, closes lumenal gate
E2 - transmembrane M1 forms cytoplasmic access tunnel to Ca2+ binding sites

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