Structural changes in the calcium pump accompanying the dissociation of calcium

  title={Structural changes in the calcium pump accompanying the dissociation of calcium},
  author={Chikashi Toyoshima and Hiromi Nomura},
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… 
The structural basis of calcium transport by the calcium pump
Functional studies and three new crystal structures of the rabbit skeletal muscle Ca2+-ATPase are presented, representing the phosphoenzyme intermediates associated withCa2+ binding, Ca2- translocation and dephosphorylation, that are based on complexes with a functional ATP analogue, beryllium fluoride and aluminium fluoride, respectively.
Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca2+‐ATPase: Insights from molecular modeling
This work uses molecular dynamics and electrostatic modeling to investigate structural and dynamical features of key intermediates in the Ca2+ binding process of the protein and indicates that uptake of the metal ions causes large structural rearrangements of theMetal binding sites.
Structural Basis for the Function of the C-Terminal Proton Release Pathway in the Calcium Pump
Calcium pump atomistic simulations demonstrate that in the protonated E2 state and the absence of initially bound water molecules, the C-terminal pore becomes hydrated in the nanosecond timescale and support the notion that the C.terminal proton release pathway is a functional element of SERCA and provide a mechanistic model for its operation in the catalytic cycle of the pump.
The Ca 2+ ATPase of the Sarco-/Endoplasmic Reticulum (SERCA): Structure and Control
The transport mechanism employed by SERCA1a from rabbit skeletal muscle has been dissected at the molecular level by several crystal structures that represent nearly all the different conformational states of the catalytic cycle of Ca2+ transport.
Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues
These structures show that the three cytoplasmic domains rearrange to move six out of ten transmembrane helices, thereby changing the affinity of the Ca2+-binding sites and the gating of the ion pathway.
Ion Pathways in the Sarcoplasmic Reticulum Ca2+-ATPase*
A model for the ion exchange mechanism in PII-ATPases including not one, but two cytoplasmic pathways working in concert is suggested.
The Mechanics of Calcium Transport
Roles for the A domain and M1–M3 in Ca2+ transport and inhibition are postulated to postulate the role of thapsigargin and phospholamban in the Ca2-ATPase activity.
The sarcolipin-bound calcium pump stabilizes calcium sites exposed to the cytoplasm
The structure of rabbit SERCA1a suggests a mechanism for selective Ca2+ loading and activation of SERCA, and provides new insight into how SLN and PLB inhibition arises from stabilization of this E1 intermediate state without bound Ca2+.
Crystal structures of the calcium pump and sarcolipin in the Mg2+-bound E1 state
The crystal structures reported here fill a gap in the structural elucidation of the reaction cycle and provide a solid basis for understanding the physiological regulation of the calcium pump.
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


Structure of the calcium pump from sarcoplasmic reticulum at 8-Å resolution
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.
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
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
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 *
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? (*)
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.