View source for 6feg


==Solution Structure of CaM/Kv7.2-hAB Complex==
<StructureSection load='6feg' size='340' side='right'caption='[[6feg]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6feg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FEG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FEG FirstGlance]. <br>
</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>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KCNQ2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CALM1, CALM, CAM, CAM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<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=6feg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6feg OCA], [http://pdbe.org/6feg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6feg RCSB], [http://www.ebi.ac.uk/pdbsum/6feg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6feg ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://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 ==
[[http://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 ==
The Kv7.2 (KCNQ2) channel is the principal molecular component of the slow voltage-gated, noninactivating K(+) M-current, a key controller of neuronal excitability. To investigate the calmodulin (CaM)-mediated Ca(2+) gating of the channel, we used NMR spectroscopy to structurally and dynamically describe the association of helices hA and hB of Kv7.2 with CaM, as a function of Ca(2+) concentration. The structures of the CaM/Kv7.2-hAB complex at two different calcification states are reported here. In the presence of a basal cytosolic Ca(2+) concentration (10-100 nM), only the N-lobe of CaM is Ca(2+)-loaded and the complex (representative of the open channel) exhibits collective dynamics on the millisecond time scale toward a low-populated excited state (1.5%) that corresponds to the inactive state of the channel. In response to a chemical or electrical signal, intracellular Ca(2+) levels rise up to 1-10 muM, triggering Ca(2+) association with the C-lobe. The associated conformational rearrangement is the key biological signal that shifts populations to the closed/inactive channel. This reorientation affects the C-lobe of CaM and both helices in Kv7.2, allosterically transducing the information from the Ca(2+)-binding site to the transmembrane region of the channel.

Structural basis and energy landscape for the Ca(2+) gating and calmodulation of the Kv7.2 K(+) channel.,Bernardo-Seisdedos G, Nunez E, Gomis C, Malo C, Villarroel A, Millet O Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2395-2400. doi:, 10.1073/pnas.1800235115. Epub 2018 Feb 20. PMID:29463698<ref>PMID:29463698</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6feg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Calmodulin 3D structures|Calmodulin 3D structures]]
*[[Potassium Channel|Potassium Channel]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Bernardo-Seisdedos, G]]
[[Category: Millet, O]]
[[Category: Villarroel, A]]
[[Category: Calcium-signalling]]
[[Category: Calmodulin]]
[[Category: Complex]]
[[Category: Metal transport]]
[[Category: Transport]]
[[Category: Voltage-gated potassium channel]]