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Comparing skeletal and cardiac calsequestrin structures and their calcium binding: a proposed mechanism for coupled calcium binding and protein polymerizationComparing skeletal and cardiac calsequestrin structures and their calcium binding: a proposed mechanism for coupled calcium binding and protein polymerization
Structural highlights
Function[CASQ2_CANFA] Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. The release of calcium bound to calsequestrin through a calcium release channel triggers muscle contraction. The skeletal muscle isoform (CASQ1) binds around 80 Ca(2+) ions, while the cardiac isoform (CASQ2) binds approximately 60 Ca(2+) ions.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCalsequestrin, 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 approximately 80 Ca(2+) ions bound per skeletal calsequestrin and approximately 60 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 light-scattering data, a mechanism of Ca(2+) binding coupled with polymerization is proposed. Comparing skeletal and cardiac calsequestrin structures and their calcium binding: a proposed mechanism for coupled calcium binding and protein polymerization.,Park H, Park IY, Kim E, Youn B, Fields K, Dunker AK, Kang C J Biol Chem. 2004 Apr 23;279(17):18026-33. Epub 2004 Feb 10. PMID:14871888[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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