Structural changes in the calcium pump accompanying the dissociation of calcium

@article{Toyoshima2002StructuralCI,
  title={Structural changes in the calcium pump accompanying the dissociation of calcium},
  author={Chikashi Toyoshima and Hiromi Nomura},
  journal={Nature},
  year={2002},
  volume={418},
  pages={605-611}
}
In skeletal muscle, calcium ions are transported (pumped) against a concentration gradient from the cytoplasm into the sarcoplasmic reticulum, an intracellular organelle. This causes muscle cells to relax after cytosolic calcium increases during excitation. The Ca2+ ATPase that carries out this pumping is a representative P-type ion-transporting ATPase. Here we describe the structure of this ion pump at 3.1 Å resolution in a Ca2+-free (E2) state, and compare it with that determined previously… 
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Ion pumping by calcium ATPase of sarcoplasmic reticulum.
  • C. Toyoshima
  • Biology
    Advances in experimental medicine and biology
  • 2007
Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum (SERCA1a) is an integral membrane protein of 110K and the best characterised member of the P-type (or E1/E2-type) ion translocating ATPases. It
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References

SHOWING 1-10 OF 59 REFERENCES
Structure of the calcium pump from sarcoplasmic reticulum at 8-Å resolution
TLDR
A distinct cavity leads to the putative calcium-binding site, providing a plausible path for calcium release to the lumen of the sarcoplasmic reticulum.
A structural model for the catalytic cycle of Ca(2+)-ATPase.
TLDR
It is hypothesized that both the nucleotide-binding and beta-sheet domains are highly mobile and driven by Brownian motion to elicit phosphoenzyme formation and calcium transport, respectively, and the reaction cycle of Ca(2+)-ATPase would have elements of a Brownian ratchet.
Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution
TLDR
Comparison with a low-resolution electron density map of the enzyme in the absence of calcium and with biochemical data suggests that large domain movements take place during active transport.
Nature and site of phospholamban regulation of the Ca2+ pump of sarcoplasmic reticulum
TLDR
It is shown that phospholamban is an endogenous inhibitor that is removed from the ATPase by phosphorylation, and localized the site of interaction to a single peptide isolated after cyanogen bromide cleavage of the ATP enzyme.
The Mechanism of Ca 2 1 Transport by Sarco ( Endo ) plasmic Reticulum Ca 2 1-ATPases *
TLDR
SERCA enzymes are typical of the class of P-type ATPases, which form a phosphoprotein intermediate and undergo conformational changes during the course of ATP hydrolysis, and some of the conformational states can be stabilized by adjustment of reaction conditions or through mutagenesis.
Do Transmembrane Segments in Proteolyzed Sarcoplasmic Reticulum Ca2+-ATPase Retain Their Functional Ca2+ Binding Properties after Removal of Cytoplasmic Fragments by Proteinase K? (*)
TLDR
It is concluded that in the absence of Ca2+, the complex of membrane-spanning segments in proteolyzed Ca2+-ATPase is labile, probably because of relatively free movement or rearrangement of individual segments.
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