Sandbox Reserved 820: Difference between revisions

The back-to-back form is stabilized by intermolecular interactions between the <scene name='56/568018/Oligomere_and_ligand/6'>α4 helix of the domain II</scene> and the <scene name='56/568018/Oligomere_and_ligand/7'>α3 helix of the domain I</scene> (<scene name='56/568018/Oligomere_and_ligand/8'>together</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> 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> There is also a hydrogen bond between Ala 82 and Asn 22. This dimerisation induces a very electronegative pocket at the C-terminal region which enables the binding of Ca2+.<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>

Each monomere of CASQ2 can bind between 18 to 50 Ca2+. The Ca2+ ions bind to two or more acidic amino acids like <scene name='56/568018/Glu/2'>Glutamate</scene> or <scene name='56/568018/Asp/3'>Aspartate</scene>. These amino acids are mainly outside the CASQ2 or in the C-terminal region. It had been shown that Ca2+ binds to an Asp-rich region on the C-terminal domain. <!-- METTRE DU VERT MAIS LE CT N'EST PAS DISPONIBLE cf: http://www.rcsb.org/pdb/explore/remediatedSequence.do?structureId=2VAF&bionumber=1 -->When CASQ2 form homooligomers, Ca2+ can bind in the electronegative pocket due to the front-to-front form and back-to-back form.<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 Ca2+‡ and interacts with triadin (Shin et al., 2000) http://www.sciencedirect.com/science/article/pii/S0014579300022468</ref>

Ca2+ is not the only ion which can bind to the CASQ2. One of them is Mg2+. The affinity is for Mg2+ is lower than the affinity for Ca2+ however the number of Ca2+ decrease. Another ion is H+. When the pH is low, more H+ will bind to the acidic amino acids and they can not bind Ca2+ anymore.<ref name="Calsequestrin and the calcium release channel of skeletal and cardiac muscle (Beard et Al., 2004)">PMID:15050380</ref>

CASQ2 is 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 as well as Juctin can bind to CASQ2 because of its KEKE motif between the 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> The binding site of CASQ2 for the both protein is the 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>

When CASQ2 binds to Triadin and Junctin, it induces the inhibition of RyR and when CASQ2 unbinds Triadin and Junctin , it induces the activation of Ryr and an efflux of Ca2+ 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 Ca2+ 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>