View source for 8qz4


==Crystal structure of human two pore domain potassium ion channel TREK-2 (K2P10.1) in complex with an activatory nanobody (Nb76)==
<StructureSection load='8qz4' size='340' side='right'caption='[[8qz4]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qz4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QZ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QZ4 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BA:BARIUM+ION'>BA</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=8qz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qz4 OCA], [https://pdbe.org/8qz4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qz4 RCSB], [https://www.ebi.ac.uk/pdbsum/8qz4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qz4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KCNKA_HUMAN KCNKA_HUMAN] Outward rectifying potassium channel. Produces rapidly activating and non-inactivating outward rectifier K(+) currents. Activated by arachidonic acid and other naturally occurring unsaturated free fatty acids.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Potassium channels of the Two-Pore Domain (K2P) subfamily, KCNK1-KCNK18, play crucial roles in controlling the electrical activity of many different cell types and represent attractive therapeutic targets. However, the identification of highly selective small molecule drugs against these channels has been challenging due to the high degree of structural and functional conservation that exists not only between K2P channels, but across the whole K(+) channel superfamily. To address the issue of selectivity, here we generate camelid antibody fragments (nanobodies) against the TREK-2 (KCNK10) K2P K(+) channel and identify selective binders including several that directly modulate channel activity. X-ray crystallography and CryoEM data of these nanobodies in complex with TREK-2 also reveal insights into their mechanisms of activation and inhibition via binding to the extracellular loops and Cap domain, as well as their suitability for immunodetection. These structures facilitate design of a biparatropic inhibitory nanobody with markedly improved sensitivity. Together, these results provide important insights into TREK channel gating and provide an alternative, more selective approach to modulation of K2P channel activity via their extracellular domains.

Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation.,Rodstrom KEJ, Cloake A, Sormann J, Baronina A, Smith KHM, Pike ACW, Ang J, Proks P, Schewe M, Holland-Kaye I, Bushell SR, Elliott J, Pardon E, Baukrowitz T, Owens RJ, Newstead S, Steyaert J, Carpenter EP, Tucker SJ Nat Commun. 2024 May 16;15(1):4173. doi: 10.1038/s41467-024-48536-2. PMID:38755204<ref>PMID:38755204</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8qz4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Ang J]]
[[Category: Arrowsmith CH]]
[[Category: Baronina A]]
[[Category: Bountra C]]
[[Category: Burgess-Brown NA]]
[[Category: Bushell SR]]
[[Category: Carpenter EP]]
[[Category: Chalk R]]
[[Category: Edwards AM]]
[[Category: Mukhopadhyay SMM]]
[[Category: Pardon E]]
[[Category: Pike ACW]]
[[Category: Rodstrom KEJ]]
[[Category: Steyaert J]]
[[Category: Tucker SJ]]