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| <StructureSection load='7cr0' size='340' side='right'caption='[[7cr0]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='7cr0' size='340' side='right'caption='[[7cr0]], [[Resolution|resolution]] 3.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7cr0]] 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=7CR0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7CR0 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[7cr0]] 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=7CR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CR0 FirstGlance]. <br> |
| </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> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</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=7cr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cr0 OCA], [http://pdbe.org/7cr0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cr0 RCSB], [http://www.ebi.ac.uk/pdbsum/7cr0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cr0 ProSAT]</span></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=7cr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cr0 OCA], [https://pdbe.org/7cr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cr0 RCSB], [https://www.ebi.ac.uk/pdbsum/7cr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cr0 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.
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| 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>
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| </div>
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| <div class="pdbe-citations 7cr0" style="background-color:#fffaf0;"></div>
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| == 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]]
| |