Structure and Function of the Calcium Pump

Stokes, David L.; Green, N Michael

doi:10.1146/annurev.biophys.32.110601.142433

Cited by 88 publications

(68 citation statements)

References 107 publications

(80 reference statements)

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“…DISCUSSION The affinities of the catalytic-and regulatory nucleotidebinding sites on SERCa1a for ATP (2-5 M and 0.3-1 mM, respectively, (38) are very similar to the K m and K H of scallop Ca-ATPase found here. There is much evidence for two separate binding sites for nucleotide on each Ca-ATPase polypeptide chain (8,39,40), with one of the sites functioning as an allosteric regulator site and the other as the active (catalytic) site. Thus, there are two potential nucleotide-binding sites on the scallop Ca-ATPase that have to be taken into consideration with regard to stabilization of the scallop A and B fragments in the E 1 form of the Ca-ATPase by P i , AMP-PNP, AMP-PCP, and ADP.…”

Section: Resultsmentioning

confidence: 99%

Effect of Orthophosphate, Nucleotide Analogues, ADP, and Phosphorylation on the Cytoplasmic Domains of Ca2+-ATPase from Scallop Sarcoplasmic Reticulum

Ryan

Stokes

Chen

et al. 2004

Journal of Biological Chemistry

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The effects of orthophosphate, nucleotide analogues, ADP, and covalent phosphorylation on the tryptic fragmentation patterns of the E 1 and E 2 forms of scallop Ca-ATPase were examined. Sites preferentially cleaved by trypsin in the E 1 form of the Ca-ATPase were detected in the nucleotide (N) and phosphorylation (P) domains, as well as the actuator (A) domain. These sites were occluded in the E 2 (Ca 2؉ -free) form of the enzyme, consistent with mutual protection of the A, N, and P domains through their association into a clustered structure. Similar protection of cytoplasmic Ca 2؉ -dependent tryptic cleavage sites was observed when the catalytic binding site for substrate on the E 1 form of scallop Ca-ATPase was occupied by P i , AMP-PNP, AMP-PCP, or ADP despite the presence of saturating levels of Ca 2؉ . These results suggest that occupation of the catalytic site on E 1 can induce condensation of the cytoplasmic domains to yield a unique structural intermediate that may be related to the form of the enzyme in which the active site is prepared for phosphoryl transfer. The effect of P i on the E 2 form of the scallop Ca-ATPase was also investigated, when it was found that formation of E 2 -P led to extreme resistance toward secondary cleavage by trypsin and stabilization of enzymatic activity for long periods of time.The sarco(endo)plasmic reticulum ATPases (SERCAs) 1 transport Ca 2ϩ against an electrochemical gradient from the cytoplasm into the intracellular membranous compartment of the sarcoplasmic or endoplasmic reticulum and play a major role in Ca 2ϩ homeostasis in both muscle and non-muscle cells (1, 2). In the course of transporting Ca 2ϩ , these enzymes pass through a number of relatively well defined intermediate biochemical states that can be isolated and studied. These include forms in which the ␤-carboxyl group of a specific aspartyl residue (Asp 351 in the case of rabbit SERCA1a) is present as an acylphosphate mixed anhydride. Much of the experimental data has been interpreted in terms of the enzyme being able to exist in two basic forms: the E 1 state, in which the enzyme possesses high affinity binding sites for Ca 2ϩ and can be phosphorylated by ATP but not by P i , and the E 2 state, which possesses low affinity Ca 2ϩ sites and can be phosphorylated by P i but not by ATP (3).Comparison of the tryptic digestion patterns of rabbit SERCA1a in its Ca 2ϩ -bound and -free forms has provided some of the strongest direct evidence supporting such a model where the enzyme can exist in two fundamentally different conformational states (4 -6). Recent studies have found that the E 1 (Ca 2ϩ ) 2 form of rabbit SERCa1a shows clear structural differences to the enzyme in its vanadate-stabilized Ca 2ϩ -free (E 2 ) state (7-10). In the E 1 form, the Actuator (A) domain is isolated from the nucleotide (N) and phosphorylation (P) domains, whereas in the E 2 form all three domains are clustered together.The Ca-ATPase from the cross-striated part of the adductor muscle of the sea scallop has been the subject of a ...

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Section: Resultsmentioning

confidence: 99%

Effect of Orthophosphate, Nucleotide Analogues, ADP, and Phosphorylation on the Cytoplasmic Domains of Ca2+-ATPase from Scallop Sarcoplasmic Reticulum

Ryan

Stokes

Chen

et al. 2004

Journal of Biological Chemistry

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“…Examples include small signaling proteins, various molecular motors (Vale and Milligan 2000), ion pumps (Stokes and Green 2003), and even small ribozymes (Rueda et al 2004). The small size of some of the systems makes them suitable for detailed NMR and simulation studies, which have provided detailed insights concerning the mechanism.…”

Section: Allostery In Monomeric Systems: Chey a Response Regulator Imentioning

confidence: 99%

Allostery and cooperativity revisited

2008

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Although phenomenlogical models that account for cooperativity in allosteric systems date back to the early and mid-60's (e.g., the KNF and MWC models), there is resurgent interest in the topic due to the recent experimental and computational studies that attempted to reveal, at an atomistic level, how allostery actually works. In this review, using systems for which atomistic simulations have been carried out in our groups as examples, we describe the current understanding of allostery, how the mechanisms go beyond the classical MWC/Pauling-KNF descriptions, and point out that the ''new view'' of allostery, emphasizing ''population shifts,'' is, in fact, an ''old view.'' The presentation offers not only an up-to-date description of allostery from a theoretical/computational perspective, but also helps to resolve several outstanding issues concerning allostery.

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“…During recent years, complex kinetic SERCA models, which include the binding and release of calcium and the change of conformation powered by ATP, have been presented. Among these schemes are, for example, descriptions with two (Matsuoka et al 2003;Higgins et al 2006), four (MacLennan et al 1997;Matsuoka et al 2003;Higgins et al 2006) and six transitional states (Dode et al 2002;Stokes & Green 2003;Yano et al 2004; figure 2), corresponding to various conformational states during the transport cycle.…”

Section: (C ) Models Incorporating the Buffering Of Calciummentioning

confidence: 99%

Modelling sarcoplasmic reticulum calcium ATPase and its regulation in cardiac myocytes

Koivumäki

Takalo

Korhonen

et al. 2009

Phil. Trans. R. Soc. A.

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When developing large-scale mathematical models of physiology, some reduction in complexity is necessarily required to maintain computational efficiency. A prime example of such an intricate cell is the cardiac myocyte. For the predictive power of the cardiomyocyte models, it is vital to accurately describe the calcium transport mechanisms, since they essentially link the electrical activation to contractility. The removal of calcium from the cytoplasm takes place mainly by the Na C /Ca 2C exchanger, and the sarcoplasmic reticulum Ca 2C ATPase (SERCA). In the present study, we review the properties of SERCA, its frequency-dependent and b-adrenergic regulation, and the approaches of mathematical modelling that have been used to investigate its function. Furthermore, we present novel theoretical considerations that might prove useful for the elucidation of the role of SERCA in cardiac function, achieving a reduction in model complexity, but at the same time retaining the central aspects of its function. Our results indicate that to faithfully predict the physiological properties of SERCA, we should take into account the calcium-buffering effect and reversible function of the pump. This 'uncomplicated' modelling approach could be useful to other similar transport mechanisms as well.

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Structure and Function of the Calcium Pump

Cited by 88 publications

References 107 publications

Effect of Orthophosphate, Nucleotide Analogues, ADP, and Phosphorylation on the Cytoplasmic Domains of Ca2+-ATPase from Scallop Sarcoplasmic Reticulum

Effect of Orthophosphate, Nucleotide Analogues, ADP, and Phosphorylation on the Cytoplasmic Domains of Ca2+-ATPase from Scallop Sarcoplasmic Reticulum

Allostery and cooperativity revisited

Modelling sarcoplasmic reticulum calcium ATPase and its regulation in cardiac myocytes

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