2be6

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:24, 22 May 2024) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_2be6| PDB=2be6 | SCENE= }}
 
-
===2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex===
 
-
{{ABSTRACT_PUBMED_16299511}}
 
-
==Disease==
+
==2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex==
-
[[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>
+
<StructureSection load='2be6' size='340' side='right'caption='[[2be6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2be6]] is a 6 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=2BE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BE6 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]] 2&#8491;</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=NI:NICKEL+(II)+ION'>NI</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=2be6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2be6 OCA], [https://pdbe.org/2be6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2be6 RCSB], [https://www.ebi.ac.uk/pdbsum/2be6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2be6 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/be/2be6_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=2be6 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Changes in activity-dependent calcium flux through voltage-gated calcium channels (Ca(V)s) drive two self-regulatory calcium-dependent feedback processes that require interaction between Ca(2+)/calmodulin (Ca(2+)/CaM) and a Ca(V) channel consensus isoleucine-glutamine (IQ) motif: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Here, we report the high-resolution structure of the Ca(2+)/CaM-Ca(V)1.2 IQ domain complex. The IQ domain engages hydrophobic pockets in the N-terminal and C-terminal Ca(2+)/CaM lobes through sets of conserved 'aromatic anchors.' Ca(2+)/N lobe adopts two conformations that suggest inherent conformational plasticity at the Ca(2+)/N lobe-IQ domain interface. Titration calorimetry experiments reveal competition between the lobes for IQ domain sites. Electrophysiological examination of Ca(2+)/N lobe aromatic anchors uncovers their role in Ca(V)1.2 CDF. Together, our data suggest that Ca(V) subtype differences in CDI and CDF are tuned by changes in IQ domain anchoring positions and establish a framework for understanding CaM lobe-specific regulation of Ca(V)s.
-
==Function==
+
Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex.,Van Petegem F, Chatelain FC, Minor DL Jr Nat Struct Mol Biol. 2005 Dec;12(12):1108-15. Epub 2005 Nov 20. PMID:16299511<ref>PMID:16299511</ref>
-
[[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>
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[2be6]] 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=2BE6 OCA].
+
</div>
 +
<div class="pdbe-citations 2be6" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
-
*[[Calmodulin|Calmodulin]]
+
*[[Calmodulin 3D structures|Calmodulin 3D structures]]
-
*[[Ion channels|Ion channels]]
+
*[[Ion channels 3D structures|Ion channels 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:016299511</ref><references group="xtra"/><references/>
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Chatelain, F C.]]
+
[[Category: Large Structures]]
-
[[Category: Minor, D L.]]
+
[[Category: Chatelain FC]]
-
[[Category: Petegem, F Van.]]
+
[[Category: Minor Jr DL]]
-
[[Category: Calcium channel]]
+
[[Category: Van Petegem F]]
-
[[Category: Calcium-dependent]]
+
-
[[Category: Calmodulin]]
+
-
[[Category: Facilitation]]
+
-
[[Category: Gating]]
+
-
[[Category: Inactivation]]
+
-
[[Category: Iq domain]]
+
-
[[Category: Membrane protein]]
+
-
[[Category: Voltage-gated]]
+

Current revision

2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex

PDB ID 2be6

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2be6"
Personal tools