2lqc
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2lqc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LQC FirstGlance]. <br> | <table><tr><td colspan='2'>[[2lqc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LQC 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='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=2lqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lqc OCA], [https://pdbe.org/2lqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lqc RCSB], [https://www.ebi.ac.uk/pdbsum/2lqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lqc 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=2lqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lqc OCA], [https://pdbe.org/2lqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lqc RCSB], [https://www.ebi.ac.uk/pdbsum/2lqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lqc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == 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> | [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> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | It is well-known that the opening of L-type voltage-gated calcium channels can be regulated by calmodulin (CaM). One of the main regulatory mechanisms is calcium-dependent inactivation (CDI), where binding of apo-CaM to the cytoplasmic C-terminal domain of the channel can effectively sense an increase in the local calcium ion concentration. Calcium-bound CaM can bind to the IQ-motif region of the C-terminal region and block the calcium channel, thereby providing a negative feedback mechanism that prevents the rise of cellular calcium concentrations over physiological limits. Recently, an additional Ca(2+)/CaM-binding motif (NSCaTE, N-terminal spatial Ca(2+) transforming element) was identified in the amino terminal cytoplasmic region of Ca(v)1.2 and Ca(v)1.3. This motif exists only in Ca(v)1.2 and Ca(v)1.3 channels, and a pronounced N-lobe (Ca(2+)/CaM) CDI effect was found for Ca(v)1.3. To understand the molecular basis of this interaction, the complexes of Ca(2+)/CaM with the biosynthetically produced N-terminal region (residues 1-68) and NSCaTE peptide (residues 48-68) were investigated. We discovered that the NSCaTE motif in the N-terminal cytoplasmic region adopts an alpha-helical conformation, most likely due to its high alanine content. Additionally, the complex exhibits an unusual 1:2 protein:peptide stoichiometry when bound to Ca(2+)-CaM, and the N-lobe of CaM has a much stronger affinity for the peptide than the C-lobe. The complex structures of the isolated N- and C-lobe of Ca(2+)/CaM and the NSCaTE peptide were determined by nuclear magnetic resonance spectroscopy and data-driven protein-docking methods. Moreover, we also demonstrated that calcium binding protein 1, which competes with CaM for binding to the C-terminal cytoplasmic domain, binds only weakly to the NSCaTE region. The structures provide insights into the possible roles of this motif in the calcium regulatory network. Our study provides structural evidence for the CaM-bridge model proposed in previous studies. | ||
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| - | Structural basis for the regulation of L-type voltage-gated calcium channels: interactions between the N-terminal cytoplasmic domain and Ca(2+)-calmodulin.,Liu Z, Vogel HJ Front Mol Neurosci. 2012;5:38. Epub 2012 Apr 12. PMID:22518098<ref>PMID:22518098</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 2lqc" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
NMR solution structure of a Ca2+-Calmodulin with a binding motif (NSCaTE) peptide from the N-terminal cytoplasmic domain of the L-type Voltage-Cated Calcium Channel alpha1C subunit
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