Polymerization of Calsequestrin

Park, HaJeung; Wu, Si; Dunker, A. Keith; Kang, Chulho

doi:10.1074/jbc.m300120200

Cited by 114 publications

(52 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this crystal lattice packing, our previous static light-scattering experiments with ⌬C27 cCSQ solutions gave an apparent molecular weight corresponding to a dimer (13).…”

Section: Resultssupporting

confidence: 52%

“…Previously, we determined the cation dependence of the apparent molecular weight of ⌬C27 cCSQ using size exclusion chromatography equipped with static light-scattering instruments (13). This truncation mutant shows the same Ca 2ϩ -dependent dimerization pattern after an increase in calcium ions despite its 27 fewer acidic residues in its tail but stays in the dimer state and does not show any further Ca 2ϩ -dependent polymerization as observed in the case of wild-type cCSQ.…”

Section: Resultsmentioning

confidence: 99%

“…4B). Previously, we showed that deletion of the first 13 residues (⌬N13 cCSQ) leads to a high molecular weight aggregate, probably due to random interactions among CSQ molecules (13). All but 3 of these 13 residues are identical between canine cCSQ and skeletal sCSQ (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These linear polymers provide a reasonable basis for both the crystalline arrays seen in vivo and the needle-shaped crystals often grown in vitro in the presence of Ca 2ϩ . We also reported that oligomerization is Ca 2ϩ /K ϩ -dependent and proposed several ways this dynamic polymerization may have biological significance (13). According to our proposal, the front-to-front and back-to-back contacts between the CSQ subunits permit formation of a Ca 2ϩ -dependent linear polymer that is inhibited as the concentration of monovalent ion, K ϩ , increases.…”

mentioning

confidence: 98%

See 3 more Smart Citations

Comparing Skeletal and Cardiac Calsequestrin Structures and Their Calcium Binding

Park

Kim

et al. 2004

Journal of Biological Chemistry

Self Cite

131

View full text Add to dashboard Cite

Calsequestrin, the major calcium storage protein of both cardiac and skeletal muscle, binds and releases large numbers of Ca 2؉ ions for each contraction and relaxation cycle. Here we show that two crystal structures for skeletal and cardiac calsequestrin are nearly superimposable not only for their subunits but also their front-to-front-type dimers. Ca 2؉ binding curves were measured using atomic absorption spectroscopy. This method enables highly accurate measurements even for Ca 2؉ bound to polymerized protein. The binding curves for both skeletal and cardiac calsequestrin were complex, with binding increases that correlated with protein dimerization, tetramerization, and oligomerization. The Ca 2؉ binding capacities of skeletal and cardiac calsequestrin are directly compared for the first time, with ϳ80 Ca 2؉ ions bound per skeletal calsequestrin and ϳ60 Ca 2؉ ions per cardiac calsequestrin, as compared with net charges for these molecules of ؊80 and ؊69, respectively. Deleting the negatively charged and disordered C-terminal 27 amino acids of cardiac calsequestrin results in a 50% reduction of its calcium binding capacity and a loss of Ca 2؉ -dependent tetramer formation. Based on the crystal structures of rabbit skeletal muscle calsequestrin and canine cardiac calsequestrin, Ca 2؉ binding capacity data, and previous lightscattering data, a mechanism of Ca 2؉ binding coupled with polymerization is proposed.Calsequestrin (CSQ) 1 binds and releases large quantities of Ca 2ϩ through its high capacity (40 -50 mol of Ca 2ϩ ion per molecule) and relatively low affinity interactions with Ca 2ϩ (K d ϭ 1 mM) (1). Because of this Ca 2ϩ -buffering capacity of CSQ in the lumenal space, the concentration of free Ca 2ϩ in the sarcoplasmic reticulum (SR) can be maintained below the inhibitory level of the Ca 2ϩ pump (1 mM), and simultaneously, the SR can maintain the ability to rapidly deliver a high capacity Ca 2ϩ signal to the cytoplasm. Even though the lumenal space is minuscule compared with the extracellular space, the high concentrations (ϳ100 mg/ml) of CSQ make the SR an efficient storage compartment for Ca 2ϩ (2).CSQ is associated physically with the RyR protein by a nucleation event that involves CSQ binding to the basic lumenal domains of triadin (3) or junctin (4). These two proteins interact with RyR in the junctional face region of the SR, and this network of interacting proteins assures that high concentrations of Ca 2ϩ are stored very near to the site of Ca 2ϩ release. Ca 2ϩ release from CSQ through the Ca 2ϩ release channel is regulatory but not limiting.The Ca 2ϩ binding and dissociation mechanisms of CSQ are not yet clearly understood. Ca 2ϩ binding sites in CSQ are supposed to be very different from those in the Ca 2ϩ pump (sarco(endo)plasmic reticulum calcium ATPase (SERCA)), calmodulin, and troponin C. CSQ sites need to be made and broken but not over the low cytosolic Ca 2ϩ concentration range or with the same stoichiometry and precision as those formed and subsequently disrupted in the Ca 2ϩ pump or...

show abstract

“…Consistent with this crystal lattice packing, our previous static light-scattering experiments with ⌬C27 cCSQ solutions gave an apparent molecular weight corresponding to a dimer (13).…”

Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 98%

See 2 more Smart Citations

Comparing Skeletal and Cardiac Calsequestrin Structures and Their Calcium Binding

Park

Kim

et al. 2004

Journal of Biological Chemistry

Self Cite

131

View full text Add to dashboard Cite

show abstract

“…The rabbit CASQ1 and the dog CASQ2 have been crystallized (6,7); results of crystallization studies shown that the casq monomer was found to be constituted by three almost identical domains (I, II, and III) similar to that of Escherichia coli thioredoxin domain. It was found that CASQ polymerizes in response to rising concentrations of Ca 2ϩ in the lumen of the SR, to form a homotetrameric complex (10 M to 1 mM) and at higher concentrations of polymers, in concentrations higher than 10 mM the CASQ polymer dissociates from the Ca 2ϩ releasing channel (8).…”

mentioning

confidence: 99%

Transcriptional Analysis of the Human Cardiac Calsequestrin Gene in Cardiac and Skeletal Myocytes

Reyes-Juárez

Juárez-Rubí

Rodrı́guez

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Calsequestrin is the main calcium-binding protein inside the sarcoplasmic reticulum of striated muscle. In mammals, the cardiac calsequestrin gene (casq2) mainly expresses in cardiac muscle and to a minor extent in slow-twitch skeletal muscle and it is not expressed in non-muscle tissues. This work is the first study on the transcriptional regulation of the casq2 gene in cardiac and skeletal muscle cells. The sequence of the casq2 genes proximal promoter (180 bp) of mammals and avians is highly conserved and contains one TATA box, one CArG box, one E-box, and one myocyte enhancer factor 2 (MEF-2) site. We cloned the human casq2 gene 5 -regulatory region into a luciferase reporter expression vector. By functional assays we showed that a construct containing the first 288 bp of promoter was up-regulated during myogenic differentiation of Sol8 cells and had higher transcriptional activity compared with longer constructs. In neonatal rat cardiac myocytes, the larger construct containing 3.2 kb showed the highest transcriptional activity, demonstrating that the first 288 bp are sufficient to confer muscle specificity, whereas distal sequences may act as a cardiacspecific enhancer. Electrophoretic mobility shift assay studies demonstrated that the proximal MEF-2 and CArG box sequences were capable of binding MEF-2 and serum response factor, respectively, whereas the E-box did not show binding properties. Functional studies demonstrated that site-directed mutagenesis of the proximal MEF-2 and CArG box sites significantly decreased the transcription of the gene in cardiac and skeletal muscle cells, indicating that they are important to drive cardiac and skeletal musclespecific transcription of the casq2 gene.

show abstract

Calsequestrin

Kang¹

2004

Handbook of Metalloproteins

View full text Add to dashboard Cite

The contraction/relaxation of the muscle cell is controlled by the transient increase/decrease of Ca 2+ concentration. A large fraction of this Ca 2+ is stored in and released from the sarcoplasmic reticulum (SR) by the presence of high concentrations of an acidic protein, calsequestrin, in the lumen of the junctional terminal cisternae of SR. Calsequestrin binds and releases large quantities of Ca 2+ ion rapidly: about 40 to 50 ions per molecule with a binding constant of approximately 1 mM under physiological conditions. The cation binding by calsequestrin is nonspecific and the Ca 2+ binding sites incorporate the numerous acidic residues that comprise over one‐third of the total residues. The crystal structure of calsequestrin shows that it is made up of three domains, each with a thioredoxin fold. Ca 2+ ions are bound on the protein surface and between domains. Two distinct dimerization contacts in calsequestrin crystals suggested a mechanism for Ca 2+ regulation resulting from the occurrence of coupled Ca 2+ binding and protein polymerization. Ca 2+ ‐induced formation of one contact was proposed to lead to dimerization followed by Ca 2+ ‐induced formation of the second contact to bring about polymerization. Strong cooperative calcium binding accompanies the polymerization of calsequestrin into insoluble, extended, and often needle‐like structures. The polymerization of calsequestrin also provides a highly charged surface onto which calcium is adsorbed. A sparingly soluble ion such as Ca 2+ would tend to spread over the surface of the polymer, forming a readily exchangeable film. The propensity of Ca 2+ ‐bound calsequestrin to form linear structures would make Ca 2+ dissociation and diffusion a more rapid event.

show abstract

Polymerization of Calsequestrin

Cited by 114 publications

References 29 publications

Comparing Skeletal and Cardiac Calsequestrin Structures and Their Calcium Binding

Comparing Skeletal and Cardiac Calsequestrin Structures and Their Calcium Binding

Transcriptional Analysis of the Human Cardiac Calsequestrin Gene in Cardiac and Skeletal Myocytes

Calsequestrin

Contact Info

Product

Resources

About