Sandbox Reserved 820: Difference between revisions
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=== Monomere Structure === | === Monomere Structure === | ||
Each monomer is divided in <scene name='56/568018/Monomer_structure/5'>3 thioredoxin domains (TRX)</scene>: <scene name='56/568018/Monomer_structure/ | Each monomer is divided in <scene name='56/568018/Monomer_structure/5'>3 thioredoxin domains (TRX)</scene>: <scene name='56/568018/Monomer_structure/9'>the N-term</scene>, <scene name='56/568018/Monomer_structure/10'>the middle</scene> and the <scene name='56/568018/Monomer_structure/11'>C-term</scene> domains. Each of these has a regular structure: a <scene name='56/568018/Beta_sheet/4'>5 strands beta sheet core</scene> surrounded by <scene name='56/568018/Alpha_helix/3'>4 alpha helices</scene>.<ref name="Martin">PMID:7788290</ref> | ||
Usually these domains are involved in redox phenomena, which lead to disulfide bounds creation. Here these domains are inactive but play an important role in the polymerization of CASQ2.<ref name="Monomere structure">NCBI Structure Ressource: CASQ2 calsequestrin 2 http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?ascbin=8&maxaln=10&seltype=2&uid=239372&querygi=429544235&aln=1,227,0,109</ref> | Usually these domains are involved in redox phenomena, which lead to disulfide bounds creation. Here these domains are inactive but play an important role in the polymerization of CASQ2.<ref name="Monomere structure">NCBI Structure Ressource: CASQ2 calsequestrin 2 http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?ascbin=8&maxaln=10&seltype=2&uid=239372&querygi=429544235&aln=1,227,0,109</ref> | ||
Finally, the C-term Asp-rich end is intrisically disordered ''(therefore, the C-term end cannot be represented in 3D structures)''. <ref name="Polymerization of Calsequestrin: IMPLICATIONS FOR Ca2+ and REGULATION">Polymerization of Calsequestrin: IMPLICATIONS FOR Ca2+ and REGULATION (Park et al., 2003) http://www.jbc.org/content/278/18/16176.full.pdf+html</ref> | Finally, the C-term Asp-rich end is intrisically disordered ''(therefore, the C-term end cannot be represented in 3D structures)''. <ref name="Polymerization of Calsequestrin: IMPLICATIONS FOR Ca2+ and REGULATION">Polymerization of Calsequestrin: IMPLICATIONS FOR Ca2+ and REGULATION (Park et al., 2003) http://www.jbc.org/content/278/18/16176.full.pdf+html</ref> | ||
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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/15'>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 | 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/15'>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> | ||