Evidence and sources

Measurements

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Big picture numbers

Structures

• 1SU4
  E1 with two calcium ions

  The reference state of the cycle and the hero of the scene. Its primary citation is the 2000 Nature structure; this entry is the 2.4 A version. X-ray diffraction, 2.4 Å.
• 3W5A
  E1 with magnesium, sarcolipin bound

  The resting state that starts the cycle, and the only structure that shows sarcolipin in place. X-ray diffraction, 3.01 Å.
• 1T5S
  Calcium-bound E1 with an ATP analogue

  Shows the closed cytoplasmic headpiece with calcium occluded, one step before phosphoryl transfer. X-ray diffraction, 2.6 Å.
• 1VFP
  Calcium-bound E1 with AMPPCP, second crystal form

  Independent view of the same nucleotide-bound state. Useful as a cross-check on the N-to-P domain bridge. X-ray diffraction, 2.9 Å.
• 1T5T
  Phosphoryl transfer transition state

  Freezes the chemistry: two magnesium ions, ADP leaving, the phosphoryl group on the aspartate. X-ray diffraction, 2.9 Å.
• 2ZBD
  Phosphoryl transfer transition state at 2.4 A

  The highest-resolution view of the same transition state, and it carries a bound phospholipid. X-ray diffraction, 2.4 Å.
• 3BA6
  Calcium-bound phosphoenzyme

  The phosphoenzyme with calcium still inside. The next step opens the lumenal gate. X-ray diffraction, 2.8 Å.
• 3B9B
  E2P with beryllium fluoride

  The state with the lumenal exit path open and Glu 309, Glu 771 and Asn 796 exposed. Calcium has left. X-ray diffraction, 2.65 Å.
• 3B9R
  Dephosphorylation transition state, no thapsigargin

  The hydrolysis step without any inhibitor, so the scene can show dephosphorylation on the native protein. X-ray diffraction, 3 Å.
• 1XP5
  Dephosphorylation transition state with protons occluded

  The counter-ion step. This is the state the authors read as occluded protons, and it carries thapsigargin. X-ray diffraction, 3 Å.
• 1WPG
  E2 with magnesium fluoride, product state

  Highest-resolution entry in the set at 2.3 A. It anchors the lumenal gating argument. X-ray diffraction, 2.3 Å.
• 3W5C
  E2 with no inhibitor bound

  The clean E2 state. Use it, not the thapsigargin entries, when the animation must show the native return path. X-ray diffraction, 2.5 Å.
• 1IWO
  E2 locked by thapsigargin

  The drug swap in the lab panel. It also gave the first picture of the calcium-free pump. X-ray diffraction, 3.1 Å.
• 4KYT
  E2 held by phospholamban

  The regulation swap. The calcium sites are collapsed and carry no divalent cation. X-ray diffraction, 2.833 Å.
• 2ZXE
  Sodium-potassium pump, potassium-occluded state

  Side-by-side comparison. The same cycle, different cargo, and two extra subunits. X-ray diffraction, 2.4 Å.
• 3WGU
  Sodium-potassium pump before E1P

  The sibling pump caught at the same point in the cycle as SERCA 1T5T, so the two families can be morphed in parallel. X-ray diffraction, 2.8 Å.

References

1. 1Toyoshima et al., Nature 2000. Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution
2. 2Toyoshima and Nomura, Nature 2002. Structural changes in the calcium pump accompanying the dissociation of calcium
3. 3Toyoshima et al., Nature 2004. Crystal structure of the calcium pump with a bound ATP analogue
4. 4Toyoshima et al., Nature 2004. Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues
5. 5Toyoshima and Inesi, Annu Rev Biochem 2004. Structural basis of ion pumping by Ca2+-ATPase of the sarcoplasmic reticulum
6. 6Sorensen et al., Science 2004. Phosphoryl transfer and calcium ion occlusion in the calcium pump
7. 7Olesen et al., Science 2004. Dephosphorylation of the calcium pump coupled to counterion occlusion
8. 8Olesen et al., Nature 2007. The structural basis of calcium transport by the calcium pump
9. 9Toyoshima et al., Nature 2013. Crystal structures of the calcium pump and sarcolipin in the Mg2+-bound E1 state
10. 10Akin et al., J Biol Chem 2013. The structural basis for phospholamban inhibition of the calcium pump in sarcoplasmic reticulum
11. 11Cleary et al., J Biol Chem 2024. Phospholamban inhibits the cardiac calcium pump by interrupting an allosteric activation pathway
12. 12MacLennan and Kranias, Nat Rev Mol Cell Biol 2003. Phospholamban: a crucial regulator of cardiac contractility
13. 13Sagara and Inesi, J Biol Chem 1991. Inhibition of the sarcoplasmic reticulum Ca2+ transport ATPase by thapsigargin at subnanomolar concentrations
14. 14Heegaard et al., J Biol Chem 1990. Monomeric state and Ca2+ transport by sarcoplasmic reticulum Ca2+-ATPase, reconstituted with an excess of phospholipid
15. 15Seflova et al., J Membrane Biol 2026. Fluorescence lifetime spectroscopy reveals distinct allosteric mechanisms of SERCA inhibitors
16. 16Yu et al., Biophys J 1993. H+ countertransport and electrogenicity of the sarcoplasmic reticulum Ca2+ pump in reconstituted proteoliposomes
17. 17Periasamy and Kalyanasundaram, Muscle Nerve 2007. SERCA pump isoforms: their role in calcium transport and disease
18. 18Verry and Makarewich, Front Cell Dev Biol 2026. Microprotein, macro-effect: DWORF as a therapeutic strategy in heart failure
19. 19Berridge et al., Nat Rev Mol Cell Biol 2003. Calcium signalling: dynamics, homeostasis and remodelling
20. 20Bublitz et al., J Cell Sci 2011. P-type ATPases at a glance
21. 21Morth et al., Nat Rev Mol Cell Biol 2010. A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps
22. 22Shinoda et al., Nature 2009. Crystal structure of the sodium-potassium pump at 2.4 A resolution
23. 23Kanai et al., Nature 2013. Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state