View source for 6cno


==Cryo-EM structure of the human SK4/calmodulin channel complex in the Ca2+ bound state II==
<StructureSection load='6cno' size='340' side='right' caption='[[6cno]], [[Resolution|resolution]] 4.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cno]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CNO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CNO 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">KCNN4, IK1, IKCA1, KCA4, SK4 ([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=6cno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cno OCA], [http://pdbe.org/6cno PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cno RCSB], [http://www.ebi.ac.uk/pdbsum/6cno PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cno ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/KCNN4_HUMAN KCNN4_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. [[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/KCNN4_HUMAN KCNN4_HUMAN]] Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMed:18796614).<ref>PMID:17157250</ref> <ref>PMID:18796614</ref> <ref>PMID:26148990</ref>  [[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 ==
Small-conductance Ca(2+)-activated K(+) (SK) channels mediate neuron excitability and are associated with synaptic transmission and plasticity. They also regulate immune responses and the size of blood cells. Activation of SK channels requires calmodulin (CaM), but how CaM binds and opens SK channels has been unclear. Here we report cryo-electron microscopy (cryo-EM) structures of a human SK4-CaM channel complex in closed and activated states at 3.4- and 3.5-angstrom resolution, respectively. Four CaM molecules bind to one channel tetramer. Each lobe of CaM serves a distinct function: The C-lobe binds to the channel constitutively, whereas the N-lobe interacts with the S4-S5 linker in a Ca(2+)-dependent manner. The S4-S5 linker, which contains two distinct helices, undergoes conformational changes upon CaM binding to open the channel pore. These structures reveal the gating mechanism of SK channels and provide a basis for understanding SK channel pharmacology.

Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.,Lee CH, MacKinnon R Science. 2018 May 4;360(6388):508-513. doi: 10.1126/science.aas9466. PMID:29724949<ref>PMID:29724949</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6cno" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Lee, C H]]
[[Category: MacKinnon, R]]
[[Category: Calmodulin]]
[[Category: Ion channel]]
[[Category: Membrane protein]]
[[Category: Neuroscience]]