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| | <StructureSection load='3o78' size='340' side='right'caption='[[3o78]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='3o78' size='340' side='right'caption='[[3o78]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3o78]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O78 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3o78]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria], [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O78 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">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CR2:{(4Z)-2-(AMINOMETHYL)-4-[(4-HYDROXYPHENYL)METHYLIDENE]-5-OXO-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}ACETIC+ACID'>CR2</scene></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>, <scene name='pdbligand=CR2:{(4Z)-2-(AMINOMETHYL)-4-[(4-HYDROXYPHENYL)METHYLIDENE]-5-OXO-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}ACETIC+ACID'>CR2</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3o77|3o77]], [[3ek4|3ek4]], [[3ek7|3ek7]], [[3ek8|3ek8]], [[3ekh|3ekh]], [[3ekj|3ekj]], [[3evp|3evp]], [[3evr|3evr]], [[3evu|3evu]], [[3evv|3evv]]</div></td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/[Myosin_light-chain]_kinase [Myosin light-chain] kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.18 2.7.11.18] </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=3o78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o78 OCA], [https://pdbe.org/3o78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o78 RCSB], [https://www.ebi.ac.uk/pdbsum/3o78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o78 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=3o78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o78 OCA], [https://pdbe.org/3o78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o78 RCSB], [https://www.ebi.ac.uk/pdbsum/3o78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o78 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MYLK_CHICK MYLK_CHICK]] Phosphorylates a specific serine in the N-terminus of a myosin light chain, which leads to the formation of calmodulin/MLCK signal transduction complexes which allow selective transduction of calcium signals. | + | [https://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).<ref>PMID:16760425</ref> <ref>PMID:23893133</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref> [https://www.uniprot.org/uniprot/MYLK_CHICK MYLK_CHICK] Phosphorylates a specific serine in the N-terminus of a myosin light chain, which leads to the formation of calmodulin/MLCK signal transduction complexes which allow selective transduction of calcium signals.[https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Aequorea victoria]] |
| | + | [[Category: Gallus gallus]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Britanova, O V]] | + | [[Category: Britanova OV]] |
| - | [[Category: Chudakov, D M]] | + | [[Category: Chudakov DM]] |
| - | [[Category: Freuler, F]] | + | [[Category: Freuler F]] |
| - | [[Category: Leder, L]] | + | [[Category: Leder L]] |
| - | [[Category: Marsh, M]] | + | [[Category: Marsh M]] |
| - | [[Category: Mayr, L M]] | + | [[Category: Mayr LM]] |
| - | [[Category: Meyerhofer, M]] | + | [[Category: Meyerhofer M]] |
| - | [[Category: Stark, W]] | + | [[Category: Stark W]] |
| - | [[Category: Stettler, T]] | + | [[Category: Stettler T]] |
| - | [[Category: Strukova, L A]] | + | [[Category: Strukova LA]] |
| - | [[Category: Calcium sensor]]
| + | |
| - | [[Category: Circular permutated green fluorescent protein]]
| + | |
| - | [[Category: Fluorescent protein]]
| + | |
| - | [[Category: Genetically encoded]]
| + | |
| - | [[Category: Gfp calmodulin m13-peptide]]
| + | |
| - | [[Category: Gyg naturally modified tripeptide acts as chromophore]]
| + | |
| - | [[Category: M13-peptide]]
| + | |
| Structural highlights
Disease
CALM1_HUMAN The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.
Function
CALM1_HUMAN Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[1] [2] [3] [4] MYLK_CHICK Phosphorylates a specific serine in the N-terminus of a myosin light chain, which leads to the formation of calmodulin/MLCK signal transduction complexes which allow selective transduction of calcium signals.GFP_AEQVI Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.
Publication Abstract from PubMed
Here we report the first crystal structure of a high-contrast genetically encoded circularly permuted green fluorescent protein (cpGFP)-based Ca(2+) sensor, Case16, in the presence of a low Ca(2+) concentration. The structure reveals the positioning of the chromophore within Case16 at the first stage of the Ca(2+)-dependent response when only two out of four Ca(2+)-binding pockets of calmodulin (CaM) are occupied with Ca(2+) ions. In such a "half Ca(2+)-bound state", Case16 is characterized by an incomplete interaction between its CaM-/M13-domains. We also report the crystal structure of the related Ca(2+) sensor Case12 at saturating Ca(2+) concentration. Based on this structure, we postulate that cpGFP-based Ca(2+) sensors can form non-functional homodimers where the CaM-domain of one sensor molecule binds symmetrically to the M13-peptide of the partner sensor molecule. Case12 and Case16 behavior upon addition of high concentrations of free CaM or M13-peptide reveals that the latter effectively blocks the fluorescent response of the sensor. We speculate that the demonstrated intermolecular interaction with endogenous substrates and homodimerization can impede proper functioning of this type of Ca(2+) sensors in living cells.
The structure of Ca2+ sensor Case16 reveals the mechanism of reaction to low Ca2+ concentrations.,Leder L, Stark W, Freuler F, Marsh M, Meyerhofer M, Stettler T, Mayr LM, Britanova OV, Strukova LA, Chudakov DM, Souslova EA Sensors (Basel). 2010;10(9):8143-60. Epub 2010 Aug 30. PMID:22163646[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sanchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell. 2006 Aug;17(8):3423-34. Epub 2006 Jun 7. PMID:16760425 doi:10.1091/mbc.E06-04-0371
- ↑ Reichow SL, Clemens DM, Freites JA, Nemeth-Cahalan KL, Heyden M, Tobias DJ, Hall JE, Gonen T. Allosteric mechanism of water-channel gating by Ca-calmodulin. Nat Struct Mol Biol. 2013 Jul 28. doi: 10.1038/nsmb.2630. PMID:23893133 doi:10.1038/nsmb.2630
- ↑ Boczek NJ, Gomez-Hurtado N, Ye D, Calvert ML, Tester DJ, Kryshtal D, Hwang HS, Johnson CN, Chazin WJ, Loporcaro CG, Shah M, Papez AL, Lau YR, Kanter R, Knollmann BC, Ackerman MJ. Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G. Circ Cardiovasc Genet. 2016 Apr;9(2):136-146. doi:, 10.1161/CIRCGENETICS.115.001323. Epub 2016 Mar 11. PMID:26969752 doi:http://dx.doi.org/10.1161/CIRCGENETICS.115.001323
- ↑ Yu CC, Ko JS, Ai T, Tsai WC, Chen Z, Rubart M, Vatta M, Everett TH 4th, George AL Jr, Chen PS. Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current. Heart Rhythm. 2016 Aug;13(8):1716-23. doi: 10.1016/j.hrthm.2016.05.009. Epub 2016, May 7. PMID:27165696 doi:http://dx.doi.org/10.1016/j.hrthm.2016.05.009
- ↑ Leder L, Stark W, Freuler F, Marsh M, Meyerhofer M, Stettler T, Mayr LM, Britanova OV, Strukova LA, Chudakov DM, Souslova EA. The structure of Ca2+ sensor Case16 reveals the mechanism of reaction to low Ca2+ concentrations. Sensors (Basel). 2010;10(9):8143-60. Epub 2010 Aug 30. PMID:22163646 doi:10.3390/s100908143
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