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| - | [[Image:2f3y.gif|left|200px]]<br /><applet load="2f3y" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2f3y, resolution 1.450Å" /> | |
| - | '''Calmodulin/IQ domain complex'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Calmodulin/IQ domain complex== |
| - | Ca2+-dependent inactivation (CDI) and facilitation (CDF) of the Ca(v)1.2 Ca2+ channel require calmodulin binding to a putative IQ motif in the carboxy-terminal tail of the pore-forming subunit. We present the 1.45 A crystal structure of Ca2+-calmodulin bound to a 21 residue peptide corresponding to the IQ domain of Ca(v)1.2. This structure shows that parallel binding of calmodulin to the IQ domain is governed by hydrophobic interactions. Mutations of residues I1672 and Q1673 in the peptide to alanines, which abolish CDI but not CDF in the channel, do not greatly alter the structure. Both lobes of Ca2+-saturated CaM bind to the IQ peptide but isoleucine 1672, thought to form an intramolecular interaction that drives CDI, is buried. These findings suggest that this structure could represent the conformation that calmodulin assumes in CDF.
| + | <StructureSection load='2f3y' size='340' side='right'caption='[[2f3y]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2f3y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F3Y FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45Å</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=MG:MAGNESIUM+ION'>MG</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=2f3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f3y OCA], [https://pdbe.org/2f3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f3y RCSB], [https://www.ebi.ac.uk/pdbsum/2f3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f3y ProSAT]</span></td></tr> |
| | + | </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 == |
| | + | [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> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/2f3y_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2f3y ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==Disease== | + | ==See Also== |
| - | Known diseases associated with this structure: Cavernous malformations of CNS and retina OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Cerebral cavernous malformations-1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Leukemia, acute T-cell lymphoblastic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603025 603025]], Leukemia, acute myeloid OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603025 603025]], Timothy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114205 114205]]
| + | *[[Calmodulin 3D structures|Calmodulin 3D structures]] |
| - | | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| - | ==About this Structure== | + | == References == |
| - | 2F3Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F3Y OCA].
| + | <references/> |
| - | | + | __TOC__ |
| - | ==Reference==
| + | </StructureSection> |
| - | Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel., Fallon JL, Halling DB, Hamilton SL, Quiocho FA, Structure. 2005 Dec;13(12):1881-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16338416 16338416]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Protein complex]] | + | [[Category: Large Structures]] |
| - | [[Category: Fallon, J L.]] | + | [[Category: Fallon JL]] |
| - | [[Category: Quiocho, F A.]] | + | [[Category: Quiocho FA]] |
| - | [[Category: CA]]
| + | |
| - | [[Category: MG]]
| + | |
| - | [[Category: calcium channnel]]
| + | |
| - | [[Category: calmodulin]]
| + | |
| - | [[Category: calmodulin complex]]
| + | |
| - | [[Category: cav1 2]]
| + | |
| - | [[Category: iq domain]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:17:31 2008''
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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
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