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| | ==Solution structure of Ca2+-S100A1-RyRP12== | | ==Solution structure of Ca2+-S100A1-RyRP12== |
| - | <StructureSection load='2k2f' size='340' side='right'caption='[[2k2f]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2k2f' size='340' side='right'caption='[[2k2f]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2k2f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K2F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K2F FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2k2f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K2F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K2F FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RYR1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]), S100a1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k2f OCA], [https://pdbe.org/2k2f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k2f RCSB], [https://www.ebi.ac.uk/pdbsum/2k2f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k2f ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k2f OCA], [https://pdbe.org/2k2f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k2f RCSB], [https://www.ebi.ac.uk/pdbsum/2k2f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k2f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/S10A1_RAT S10A1_RAT]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites.
| + | [https://www.uniprot.org/uniprot/RYR2_RAT RYR2_RAT] Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) cytosolic levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.[UniProtKB:Q92736]<ref>PMID:20431056</ref> <ref>PMID:20471962</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Rattus norvegicus]] | | [[Category: Rattus norvegicus]] |
| - | [[Category: Varney, K M]] | + | [[Category: Varney KM]] |
| - | [[Category: Weber, D J]] | + | [[Category: Weber DJ]] |
| - | [[Category: Wright, N T]] | + | [[Category: Wright NT]] |
| - | [[Category: Alternative splicing]]
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| - | [[Category: Calcium binding]]
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| - | [[Category: Calcium channel]]
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| - | [[Category: Calcium transport]]
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| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Ef hand]]
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| - | [[Category: Glycoprotein]]
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| - | [[Category: Ion transport]]
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| - | [[Category: Ionic channel]]
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| - | [[Category: Membrane]]
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| - | [[Category: Metal binding protein]]
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| - | [[Category: Metal-binding]]
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| - | [[Category: Polymorphism]]
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| - | [[Category: Ryanodine receptor]]
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| - | [[Category: S100]]
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| - | [[Category: Transmembrane]]
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| - | [[Category: Transport]]
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| - | [[Category: Zinc]]
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| Structural highlights
Function
RYR2_RAT Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) cytosolic levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.[UniProtKB:Q92736][1] [2]
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 PubMed
In heart and skeletal muscle an S100 protein family member, S100A1, binds to the ryanodine receptor (RyR) and promotes Ca(2+) release. Using competition binding assays, we further characterized this system in skeletal muscle and showed that Ca(2+)-S100A1 competes with Ca(2+)-calmodulin (CaM) for the same binding site on RyR1. In addition, the NMR structure was determined for Ca(2+)-S100A1 bound to a peptide derived from this CaM/S100A1 binding domain, a region conserved in RyR1 and RyR2 and termed RyRP12 (residues 3616-3627 in human RyR1). Examination of the S100A1-RyRP12 complex revealed residues of the helical RyRP12 peptide (Lys-3616, Trp-3620, Lys-3622, Leu-3623, Leu-3624, and Lys-3626) that are involved in favorable hydrophobic and electrostatic interactions with Ca(2+)-S100A1. These same residues were shown previously to be important for RyR1 binding to Ca(2+)-CaM. A model for regulating muscle contraction is presented in which Ca(2+)-S100A1 and Ca(2+)-CaM compete directly for the same binding site on the ryanodine receptor.
S100A1 and calmodulin compete for the same binding site on ryanodine receptor.,Wright NT, Prosser BL, Varney KM, Zimmer DB, Schneider MF, Weber DJ J Biol Chem. 2008 Sep 26;283(39):26676-83. Epub 2008 Jul 23. PMID:18650434[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Guo T, Cornea RL, Huke S, Camors E, Yang Y, Picht E, Fruen BR, Bers DM. Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks. Circ Res. 2010 Jun 11;106(11):1743-52. doi: 10.1161/CIRCRESAHA.110.219816. Epub, 2010 Apr 29. PMID:20431056 doi:10.1161/CIRCRESAHA.110.219816
- ↑ Takasawa S, Kuroki M, Nata K, Noguchi N, Ikeda T, Yamauchi A, Ota H, Itaya-Hironaka A, Sakuramoto-Tsuchida S, Takahashi I, Yoshikawa T, Shimosegawa T, Okamoto H. A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene. Biochem Biophys Res Commun. 2010 Jun 25;397(2):140-5. PMID:20471962 doi:10.1016/j.bbrc.2010.05.051
- ↑ Wright NT, Prosser BL, Varney KM, Zimmer DB, Schneider MF, Weber DJ. S100A1 and calmodulin compete for the same binding site on ryanodine receptor. J Biol Chem. 2008 Sep 26;283(39):26676-83. Epub 2008 Jul 23. PMID:18650434 doi:10.1074/jbc.M804432200
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