3oxq

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{{STRUCTURE_3oxq| PDB=3oxq | SCENE= }}
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==Crystal Structure of Ca2+/CaM-CaV1.2 pre-IQ/IQ domain complex==
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===Crystal Structure of Ca2+/CaM-CaV1.2 pre-IQ/IQ domain complex===
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<StructureSection load='3oxq' size='340' side='right' caption='[[3oxq]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
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{{ABSTRACT_PUBMED_20953164}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3oxq]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OXQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OXQ FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALM, CALM1, CALM2, CALM3, CALML2, Calmodulin (CaM), CAM, CAM1, CAM2, CAM3, CAMB, CAMC, CAMIII ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CACH2, CACN2, CACNA1C, CACNL1A1, calcium channel CaV1.2, CCHL1A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3oxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oxq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oxq RCSB], [http://www.ebi.ac.uk/pdbsum/3oxq PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/CAC1C_HUMAN CAC1C_HUMAN]] Defects in CACNA1C are the cause of Timothy syndrome (TS) [MIM:[http://omim.org/entry/601005 601005]]. TS is a disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism.<ref>PMID:15454078</ref> <ref>PMID:15863612</ref> Defects in CACNA1C are the cause of Brugada syndrome type 3 (BRGDA3) [MIM:[http://omim.org/entry/611875 611875]]. A heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset.<ref>PMID:17224476</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/CAC1C_HUMAN CAC1C_HUMAN]] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.<ref>PMID:8392192</ref> <ref>PMID:7737988</ref> <ref>PMID:9013606</ref> <ref>PMID:9607315</ref> <ref>PMID:12176756</ref> <ref>PMID:17071743</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Interactions between voltage-gated calcium channels (Ca(V)s) and calmodulin (CaM) modulate Ca(V) function. In this study, we report the structure of a Ca(2+)/CaM Ca(V)1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca(2+)/CaMs and two Ca(2+)/CaM-IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca(2+)/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes Ca(V)1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca(2+)/CaMs in the complex have different properties. Ca(2+)/CaM bound to the PreIQ C-region is labile, whereas Ca(2+)/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca(2+)/CaMs can bind the Ca(V)1.2 tail simultaneously and indicate a functional role for Ca(2+)/CaM at the C-region site.
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==Disease==
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Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.,Kim EY, Rumpf CH, Van Petegem F, Arant RJ, Findeisen F, Cooley ES, Isacoff EY, Minor DL Jr EMBO J. 2010 Oct 15. PMID:20953164<ref>PMID:20953164</ref>
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[[http://www.uniprot.org/uniprot/CAC1C_HUMAN CAC1C_HUMAN]] Defects in CACNA1C are the cause of Timothy syndrome (TS) [MIM:[http://omim.org/entry/601005 601005]]. TS is a disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism.<ref>PMID:15454078</ref><ref>PMID:15863612</ref> Defects in CACNA1C are the cause of Brugada syndrome type 3 (BRGDA3) [MIM:[http://omim.org/entry/611875 611875]]. A heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset.<ref>PMID:17224476</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/CAC1C_HUMAN CAC1C_HUMAN]] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.<ref>PMID:8392192</ref><ref>PMID:7737988</ref><ref>PMID:9013606</ref><ref>PMID:9607315</ref><ref>PMID:12176756</ref><ref>PMID:17071743</ref>
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</div>
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==About this Structure==
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[[3oxq]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OXQ OCA].
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==See Also==
==See Also==
*[[Calmodulin|Calmodulin]]
*[[Calmodulin|Calmodulin]]
*[[Ion channels|Ion channels]]
*[[Ion channels|Ion channels]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020953164</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arant, R.]]
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[[Category: Arant, R]]
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[[Category: Cooley, E S.]]
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[[Category: Cooley, E S]]
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[[Category: Findeisen, F.]]
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[[Category: Findeisen, F]]
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[[Category: Isacoff, E Y.]]
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[[Category: Isacoff, E Y]]
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[[Category: Kim, E Y.]]
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[[Category: Kim, E Y]]
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[[Category: Minor, D L.]]
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[[Category: Minor, D L]]
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[[Category: Petegem, F Van.]]
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[[Category: Petegem, F Van]]
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[[Category: Rumpf, C H.]]
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[[Category: Rumpf, C H]]
[[Category: Calcium binding]]
[[Category: Calcium binding]]
[[Category: Calcium sensing]]
[[Category: Calcium sensing]]

Revision as of 07:00, 19 December 2014

Crystal Structure of Ca2+/CaM-CaV1.2 pre-IQ/IQ domain complex

3oxq, resolution 2.55Å

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