Sandbox Reserved 820: Difference between revisions
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== Calcium Binding == | == Calcium Binding == | ||
Each monomere of CASQ2 can bind between <scene name='56/568018/Oligomere_and_ligand/12'>18 to 50 Ca2+</scene>. The Ca<sup>2+</sup> ions bind to two or more acidic amino acids like <scene name='56/568018/Oligomere_and_ligand/13'>Glutamate</scene> or <scene name='56/568018/Oligomere_and_ligand/ | Each monomere of CASQ2 can bind between <scene name='56/568018/Oligomere_and_ligand/12'>18 to 50 Ca2+</scene>. The Ca<sup>2+</sup> ions bind to two or more acidic amino acids like <scene name='56/568018/Oligomere_and_ligand/13'>Glutamate</scene> or <scene name='56/568018/Oligomere_and_ligand/19'>Aspartate</scene>. These amino acids are mainly oriented outside and in the C-terminal region. It had been shown that Ca<sup>2+</sup>ions mainly bind an Asp-rich region on the disordered C-terminal domain. When CASQ2 form homooligomers, Ca<sup>2+</sup> can be bound in the electronegative pockets created by the <scene name='56/568018/Oligomere_and_ligand/17'>front-to-front</scene> and <scene name='56/568018/Oligomere_and_ligand/16'>back-to-back</scene> dimer interactions.<ref name="The asp-rich region at the carboxyl-terminus of calsequestrin binds to Ca2+ and interacts with triadin (Shin et al., 2000)">The Asp-rich region at the carboxyl-terminus of calsequestrin binds to Ca<sup>2+</sup> and interacts with triadin (Shin et al., 2000) http://www.sciencedirect.com/science/article/pii/S0014579300022468</ref> | ||
CASQ2 can also bind other ions like Mg<sup>2+</sup> or H<sup>+</sup>. The affinity for Mg<sup>2+</sup> is lower than the affinity for Ca<sup>2+</sup> however the concentration of Ca<sup>2+</sup> decreases. When the pH is low, the calcium-binding capacity of CASQ2 decreases as H<sup>+</sup> ions occupy the acidic sites and inhibit the polymerization.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">PMID:15050380</ref> | CASQ2 can also bind other ions like Mg<sup>2+</sup> or H<sup>+</sup>. The affinity for Mg<sup>2+</sup> is lower than the affinity for Ca<sup>2+</sup> however the concentration of Ca<sup>2+</sup> decreases. When the pH is low, the calcium-binding capacity of CASQ2 decreases as H<sup>+</sup> ions occupy the acidic sites and inhibit the polymerization.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">PMID:15050380</ref> | ||
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CASQ2 can be phosphorylated by three different kinases: casein kinase I (CK I), casein kinase II (CK II) and ε protein kinase C1 (εPKC1).<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> CK II is located in the SR and is able to phosphorylate Ser 378, Ser 382 and Ser 386. These residues are on the C-terminal domain.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> The consensus sequence recognized by CK II is Ser/Thr-X-X-Asp/Glu.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> The phosphorylation is more likely if there are acidic residues after this consensus sequence.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> | CASQ2 can be phosphorylated by three different kinases: casein kinase I (CK I), casein kinase II (CK II) and ε protein kinase C1 (εPKC1).<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> CK II is located in the SR and is able to phosphorylate Ser 378, Ser 382 and Ser 386. These residues are on the C-terminal domain.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> The consensus sequence recognized by CK II is Ser/Thr-X-X-Asp/Glu.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> The phosphorylation is more likely if there are acidic residues after this consensus sequence.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> | ||
The phosphorylation and | The phosphorylation and dephosphorylation of CASQ2 may provide an off/on switch for CASQ2 to regulate Ca<sup>2+</sup> capture. But there is not any proof yet.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> However it is known that phosphorylations on CASQ2 modify the interactions between CASQ2 and RyR but not between CASQ2 and Triadin and Junctin.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">http://www.ncbi.nlm.nih.gov/pubmed/15050380</ref> | ||
