Sandbox Reserved 820: Difference between revisions
No edit summary |
No edit summary |
||
| Line 30: | Line 30: | ||
The back-to-back form is stabilized by intermolecular interactions between the <scene name='56/568018/Oligomere_and_ligand/7'>α3 helix of the domain I</scene>, <scene name='56/568018/Oligomere_and_ligand/6'>α4 helix of the domain II</scene><ref name="Crystal Structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum (Wang et al., 1998)">http://www.nature.com/nsmb/journal/v5/n6/abs/nsb0698-476.html</ref>, and it has also been proved that the C-term domain is involved<ref name="c term">NCBI Structure Ressource: CASQ2 calsequestrin 2 http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi</ref> (<scene name='56/568018/Oligomere_and_ligand/9'>together</scene>). The intermolecular salt bridges are built between Glu 215 and Lys 86, Glu 216 and Lys 24, Glu 169 and Lys 85.<ref name="Crystal Structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum (Wang et al., 1998)">http://www.nature.com/nsmb/journal/v5/n6/abs/nsb0698-476.html</ref> The dimerization is also favored by a hydrogen bond between Ala 82 and Asn 22. This dimerization creates a very electronegative pocket at the C-terminal region which enables the binding of Ca<sup>2+</sup>.<ref name="Crystal Structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum (Wang et al., 1998)">http://www.nature.com/nsmb/journal/v5/n6/abs/nsb0698-476.html</ref> | The back-to-back form is stabilized by intermolecular interactions between the <scene name='56/568018/Oligomere_and_ligand/7'>α3 helix of the domain I</scene>, <scene name='56/568018/Oligomere_and_ligand/6'>α4 helix of the domain II</scene><ref name="Crystal Structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum (Wang et al., 1998)">http://www.nature.com/nsmb/journal/v5/n6/abs/nsb0698-476.html</ref>, and it has also been proved that the C-term domain is involved<ref name="c term">NCBI Structure Ressource: CASQ2 calsequestrin 2 http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi</ref> (<scene name='56/568018/Oligomere_and_ligand/9'>together</scene>). The intermolecular salt bridges are built between Glu 215 and Lys 86, Glu 216 and Lys 24, Glu 169 and Lys 85.<ref name="Crystal Structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum (Wang et al., 1998)">http://www.nature.com/nsmb/journal/v5/n6/abs/nsb0698-476.html</ref> The dimerization is also favored by a hydrogen bond between Ala 82 and Asn 22. This dimerization creates a very electronegative pocket at the C-terminal region which enables the binding of Ca<sup>2+</sup>.<ref name="Crystal Structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum (Wang et al., 1998)">http://www.nature.com/nsmb/journal/v5/n6/abs/nsb0698-476.html</ref> | ||
== 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 binds an Asp-rich region on the disordered C-terminal domain. | 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 binds 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/16'>front-to-front</scene> and <scene name='56/568018/Oligomere_and_ligand/17'>back-to-back</scene> dimer interactions.<ref name="The asp-rich region at the carboxyl-terminus of calsequestrin binds to Ca<sup>2+</sup> 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.<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.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">PMID:15050380</ref> | ||
== Interaction between CASQ2, Junctin and Triadin == | == Interaction between CASQ2, Junctin and Triadin == | ||
| Line 46: | Line 41: | ||
=== Binding sites === | === Binding sites === | ||
CASQ2 can be anchored into the membrane of SR thanks to two integral proteins: the triadin and the junctin.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">PMID:15731387</ref> Triadin and juctin can bind to CASQ2 on their KEKE motifs (amino acids 210 and 224 for the triadin).<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> Both proteins bind CASQ2 on its Asp-rich region of the C-terminal region.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> | CASQ2 can be anchored into the membrane of SR thanks to two integral proteins: the triadin and the junctin.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">PMID:15731387</ref> Triadin and juctin can bind to CASQ2 on their KEKE motifs (amino acids 210 and 224 for the triadin).<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> Both proteins bind CASQ2 on its Asp-rich region of the C-terminal region.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> | ||
Triadin and Junctin can also interact with Ryanodin Receptor | Triadin and Junctin can also interact with Ryanodin Receptor.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> | ||
The binding site of CASQ2 to Ryanodin Receptor (RyR) is unknow.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> | The binding site of CASQ2 to Ryanodin Receptor (RyR) is unknow.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> | ||
| Line 52: | Line 47: | ||
When CASQ2 binds to triadin and junctin, it induces the inhibition of RyR and then the inhibition of calcium release in the cytoplasm. On the contrary, when CASQ2 unbinds triadin and junctin, it induces the activation of Ryr and an efflux of Ca<sup>2+</sup> from the SR to the cytoplasm.<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 is free when the concentration of Ca<sup>2+</sup> is higher than 1 mM in the SR lumen.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> | When CASQ2 binds to triadin and junctin, it induces the inhibition of RyR and then the inhibition of calcium release in the cytoplasm. On the contrary, when CASQ2 unbinds triadin and junctin, it induces the activation of Ryr and an efflux of Ca<sup>2+</sup> from the SR to the cytoplasm.<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 is free when the concentration of Ca<sup>2+</sup> is higher than 1 mM in the SR lumen.<ref name="Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation (Beard et Al., 2005)">http://www.ncbi.nlm.nih.gov/pubmed/15731387</ref> | ||
== Regulation of CASQ2 == | == Regulation of CASQ2 == | ||
| Line 60: | Line 53: | ||
The phosphorylation and de-phosphorylation 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 modifies 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> | The phosphorylation and de-phosphorylation 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 modifies 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> | ||
</StructureSection> | </StructureSection> | ||