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Calcium pump

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Title: Calcium pump  
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Subject: Active transport, Cell biology
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Calcium pump

There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important for cells to maintain low concentrations of Ca2+ for proper cell signalling; thus it is necessary for the cell to employ ion pumps to remove the Ca2+.[1]

The PMCA and the sodium calcium exchanger (NCX) are together the main regulators of intracellular Ca2+ concentrations.[2]


  • Why cells need calcium pumps 1
  • Understanding calcium pumps through crystallography 2
  • How the calcium pump works 3
  • References 4

Why cells need calcium pumps

Ca2+ has many important roles as an intracellular messenger. The release of a large amount of free Ca2+ can trigger a fertilized egg to develop, skeletal muscle cells to contract, secretion by secretory cells and interactions with Ca2+ -responsive proteins like calmodulin. To maintain low concentrations of free Ca2+ in the cytosol, cells use membrane pumps like calcium ATPase found in the membranes of sarcoplasmic reticulum of skeletal muscle. These pumps are needed to provide the steep electrochemical gradient that allows Ca2+ to rush into the cytosol when a stimulus signal opens the Ca2+ channels in the membrane. The pumps are also necessary to actively pump the Ca2+ back out of the cytoplasm and return the cell to its pre-signal state.[3]

Understanding calcium pumps through crystallography

Experimental work in crystallography done by Chikashi Toyoshima and colleagues provides a model of the calcium ATPase pump found in skeletal muscle sarcoplasmic reticulum. Calcium ATPase is a member of the P-type ATPases that transport ions across a membrane against a concentration gradient. The scientists used microscopy of tubular crystals and 3D microcrystals to study this protein’s structure. The pump has a molecular mass of 110,000, shows three well separated cytoplasmic domains, with a transmembrane domain consisting of ten alpha helices, and two transmembrane binding sites for the Ca2+.
N nucleotide domain
P phosphorylation domain
A actuator domain
Transmembrane domain M1-M10 alpha helices
sarcoplasmic lumen


How the calcium pump works

Classical Theory of active transport for P-type ATPases [5]
E1 → (2H+ out, 2Ca2+ in)→ E1⋅2Ca2+ E1⋅ ATP
↑(Pi out) ↓(ADP out)
E2⋅Pi ← E2P ←(2H+ in, 2Ca2+ out) ← E1P

Data from crystallography studies by Chikashi Toyoshima applied to the above cycle [6] [7]

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


  1. ^
  2. ^
  3. ^ Bruce Alberts, Essential Cell Biology", third edition,New York, Garland Science, Taylor & Francis Group,LLC, 2010 ISBN 978-0-8153-4129-1, pages 552-553
  4. ^ Chikashi Toyoshima, 8 June 2000, "Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution", "Nature", Volume 450, pages 647-654
  5. ^ Chikashi Toyoshima, "Processing of aspartylphosphate is coupled to lumenal gating of the ion pathway in the calcium pump", The National Academy of Sciences of the USA, online before print December 5, 2007, doi: 10.1073/pnas.0709978104, PNAS December 11, 2007 vol. 104 no. 50 19831-19836,This article contains supporting information online at
  6. ^ Chikashi Toyoshima,8 AUGUST 2002,"Changes in the calcium pump accompanying the dissociation of calcium", NATURE, Volume 418,pages 605-611
  7. ^ Chikashi Toyoshima,29 JULY 2004, "Structure of the calcium pump with a bound ATP analogue", NATURE, Volume 430, pages 529-535
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