4bw5: Difference between revisions
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==Crystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1)== | |||
<StructureSection load='4bw5' size='340' side='right'caption='[[4bw5]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4bw5]] 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=4BW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BW5 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]] 3.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</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=4bw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw5 OCA], [https://pdbe.org/4bw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bw5 RCSB], [https://www.ebi.ac.uk/pdbsum/4bw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw5 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 == | |||
TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac. | |||
K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.,Dong YY, Pike AC, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S, Ruda GF, Clausen MV, Cao L, Brennan PE, Burgess-Brown NA, Sansom MS, Tucker SJ, Carpenter EP Science. 2015 Mar 13;347(6227):1256-9. doi: 10.1126/science.1261512. PMID:25766236<ref>PMID:25766236</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4bw5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Arrowsmith CH]] | |||
[[Category: Bountra C]] | |||
[[Category: Burgess-Brown N]] | |||
[[Category: Carpenter EP]] | |||
[[Category: Dong L]] | |||
[[Category: Dong YY]] | |||
[[Category: Edwards AM]] | |||
[[Category: Goubin S]] | |||
[[Category: Grieben M]] | |||
[[Category: Mackenzie A]] | |||
[[Category: Mukhopadhyay S]] | |||
[[Category: Pike ACW]] | |||
[[Category: Quigley A]] | |||
[[Category: Shintre CA]] | |||
[[Category: Shrestha L]] | |||
[[Category: Strain-Damerell C]] | |||
[[Category: Vollmar M]] | |||
[[Category: Von Delft F]] | |||
Latest revision as of 14:59, 20 December 2023
Crystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1)Crystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1)
Structural highlights
FunctionKCNKA_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. Publication Abstract from PubMedTREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac. K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.,Dong YY, Pike AC, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S, Ruda GF, Clausen MV, Cao L, Brennan PE, Burgess-Brown NA, Sansom MS, Tucker SJ, Carpenter EP Science. 2015 Mar 13;347(6227):1256-9. doi: 10.1126/science.1261512. PMID:25766236[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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