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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