View source for 6b8p


==Crystal Structure of the Mg2+/CaM:Kv7.4 (KCNQ4) AB domain complex==
<StructureSection load='6b8p' size='340' side='right'caption='[[6b8p]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6b8p]] is a 8 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=6B8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B8P 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6b8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b8p OCA], [https://pdbe.org/6b8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b8p RCSB], [https://www.ebi.ac.uk/pdbsum/6b8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b8p ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KCNQ4_HUMAN KCNQ4_HUMAN] Defects in KCNQ4 are the cause of deafness autosomal dominant type 2A (DFNA2A) [MIM:[https://omim.org/entry/600101 600101]. DFNA2A is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:10025409</ref> <ref>PMID:10369879</ref> <ref>PMID:10571947</ref> <ref>PMID:10925378</ref> <ref>PMID:21242547</ref> 
== Function ==
[https://www.uniprot.org/uniprot/KCNQ4_HUMAN KCNQ4_HUMAN] Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.<ref>PMID:11245603</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation. This C-lobe switch inhibits voltage-dependent activation of Kv7.4 and Kv7.5 but facilitates Kv7.1, demonstrating that mechanism is shared by Kv7 isoforms despite the different directions of CaM modulation. Our findings provide a unified framework for understanding how CaM controls different Kv7 isoforms and highlight the role of membrane proximal domains for controlling voltage-gated channel function. VIDEO ABSTRACT.

A Calmodulin C-Lobe Ca(2+)-Dependent Switch Governs Kv7 Channel Function.,Chang A, Abderemane-Ali F, Hura GL, Rossen ND, Gate RE, Minor DL Jr. Neuron. 2018 Feb 21;97(4):836-852.e6. doi: 10.1016/j.neuron.2018.01.035. Epub, 2018 Feb 8. PMID:29429937<ref>PMID:29429937</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6b8p" style="background-color:#fffaf0;"></div>

==See Also==
*[[Calmodulin 3D structures|Calmodulin 3D structures]]
*[[Potassium channel 3D structures|Potassium channel 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chang A]]
[[Category: Minor DL]]