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| | ==Structure of the C-linker/CNBHD of zELK channels in P 1 21 1 space group, crystallized in the presence of cAMP== | | ==Structure of the C-linker/CNBHD of zELK channels in P 1 21 1 space group, crystallized in the presence of cAMP== |
| - | <StructureSection load='3ukv' size='340' side='right' caption='[[3ukv]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='3ukv' size='340' side='right'caption='[[3ukv]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ukv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UKV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UKV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ukv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UKV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UKV FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3uk5|3uk5]], [[3ukn|3ukn]], [[3ukt|3ukt]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CH211-11O22.2-001, ELK, KCNH3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=3ukv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ukv OCA], [https://pdbe.org/3ukv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ukv RCSB], [https://www.ebi.ac.uk/pdbsum/3ukv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ukv ProSAT]</span></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=3ukv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ukv OCA], [http://pdbe.org/3ukv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ukv RCSB], [http://www.ebi.ac.uk/pdbsum/3ukv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ukv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A8WHX9_DANRE A8WHX9_DANRE] |
| - | The KCNH family of ion channels, comprising ether-a-go-go (EAG), EAG-related gene (ERG), and EAG-like (ELK) K(+)-channel subfamilies, is crucial for repolarization of the cardiac action potential, regulation of neuronal excitability and proliferation of tumour cells. The carboxy-terminal region of KCNH channels contains a cyclic-nucleotide-binding homology domain (CNBHD) and C-linker that couples the CNBHD to the pore. The C-linker/CNBHD is essential for proper function and trafficking of ion channels in the KCNH family. However, despite the importance of the C-linker/CNBHD for the function of KCNH channels, the structural basis of ion-channel regulation by the C-linker/CNBHD is unknown. Here we report the crystal structure of the C-linker/CNBHD of zebrafish ELK channels at 2.2-A resolution. Although the overall structure of the C-linker/CNBHD of ELK channels is similar to the cyclic-nucleotide-binding domain (CNBD) structure of the related hyperpolarization-activated cyclic-nucleotide-modulated (HCN) channels, there are marked differences. Unlike the CNBD of HCN, the CNBHD of ELK displays a negatively charged electrostatic profile that explains the lack of binding and regulation of KCNH channels by cyclic nucleotides. Instead of cyclic nucleotide, the binding pocket is occupied by a short beta-strand. Mutations of the beta-strand shift the voltage dependence of activation to more depolarized voltages, implicating the beta-strand as an intrinsic ligand for the CNBHD of ELK channels. In both ELK and HCN channels the C-linker is the site of virtually all of the intersubunit interactions in the C-terminal region. However, in the zebrafish ELK structure there is a reorientation in the C-linker so that the subunits form dimers instead of tetramers, as observed in HCN channels. These results provide a structural framework for understanding the regulation of ion channels in the KCNH family by the C-linker/CNBHD and may guide the design of specific drugs.
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| - | Structure of the carboxy-terminal region of a KCNH channel.,Brelidze TI, Carlson AE, Sankaran B, Zagotta WN Nature. 2012 Jan 9. doi: 10.1038/nature10735. PMID:22230959<ref>PMID:22230959</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 3ukv" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[Category: Brelidze, T I]] | + | [[Category: Large Structures]] |
| - | [[Category: Cnbd]] | + | [[Category: Brelidze TI]] |
| - | [[Category: Cnbhd]]
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| - | [[Category: Cyclic nucleotide]]
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| - | [[Category: Cyclic nucleotide-binding domain]]
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| - | [[Category: Eag]]
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| - | [[Category: Elk]]
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| - | [[Category: Erg]]
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| - | [[Category: Ion transport]]
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| - | [[Category: Kcnh]]
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| - | [[Category: Membrane protein]]
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| - | [[Category: Transport protein]]
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