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| | <StructureSection load='7cr1' size='340' side='right'caption='[[7cr1]], [[Resolution|resolution]] 3.40Å' scene=''> | | <StructureSection load='7cr1' size='340' side='right'caption='[[7cr1]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7cr1]] is a 4 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=7CR1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7CR1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7cr1]] is a 4 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=7CR1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CR1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GB9:N-(6-chloranylpyridin-3-yl)-4-fluoranyl-benzamide'>GB9</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7cr0|7cr0]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GB9:N-(6-chloranylpyridin-3-yl)-4-fluoranyl-benzamide'>GB9</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])</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=7cr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cr1 OCA], [https://pdbe.org/7cr1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cr1 RCSB], [https://www.ebi.ac.uk/pdbsum/7cr1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cr1 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7cr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cr1 OCA], [http://pdbe.org/7cr1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cr1 RCSB], [http://www.ebi.ac.uk/pdbsum/7cr1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cr1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/KCNQ2_HUMAN KCNQ2_HUMAN] |
| - | The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper-excitability. A list of synthetic compounds have been developed to directly activate KCNQ2, yet our knowledge of their activation mechanism is limited, due to lack of high-resolution structures. Here, we report cryo-electron microscopy (cryo-EM) structures of the human KCNQ2 determined in apo state and in complex with two activators, ztz240 or retigabine, which activate KCNQ2 through different mechanisms. The activator-bound structures, along with electrophysiology analysis, reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state, whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation. By accurately defining ligand-binding sites, these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms, but also provide a structural basis for drug optimization and design.
| + | |
| | | | |
| - | Molecular basis for ligand activation of the human KCNQ2 channel.,Li X, Zhang Q, Guo P, Fu J, Mei L, Lv D, Wang J, Lai D, Ye S, Yang H, Guo J Cell Res. 2020 Sep 3. pii: 10.1038/s41422-020-00410-8. doi:, 10.1038/s41422-020-00410-8. PMID:32884139<ref>PMID:32884139</ref>
| + | ==See Also== |
| - | | + | *[[Potassium channel 3D structures|Potassium channel 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 7cr1" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Guo, J]] | + | [[Category: Guo J]] |
| - | [[Category: Li, X]] | + | [[Category: Li X]] |
| - | [[Category: Lv, D]] | + | [[Category: Lv D]] |
| - | [[Category: Wang, J]] | + | [[Category: Wang J]] |
| - | [[Category: Ye, S]] | + | [[Category: Ye S]] |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Transport protein]]
| + | |
