6w7b: Difference between revisions
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==K2P2.1 (TREK-1), 0 mM K+== | ==K2P2.1 (TREK-1), 0 mM K+== | ||
<StructureSection load='6w7b' size='340' side='right'caption='[[6w7b]]' scene=''> | <StructureSection load='6w7b' size='340' side='right'caption='[[6w7b]], [[Resolution|resolution]] 3.88Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W7B FirstGlance]. <br> | <table><tr><td colspan='2'>[[6w7b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W7B FirstGlance]. <br> | ||
</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=6w7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w7b OCA], [https://pdbe.org/6w7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w7b RCSB], [https://www.ebi.ac.uk/pdbsum/6w7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w7b ProSAT]</span></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]] 3.88Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B7G:HEPTYL-BETA-D-GLUCOPYRANOSIDE'>B7G</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=OCT:N-OCTANE'>OCT</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=6w7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w7b OCA], [https://pdbe.org/6w7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w7b RCSB], [https://www.ebi.ac.uk/pdbsum/6w7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w7b ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/KCNK2_MOUSE KCNK2_MOUSE] Ion channel that contributes to passive transmembrane potassium transport. Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner. In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2 (PubMed:24496152). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (PubMed:24496152).<ref>PMID:10321245</ref> <ref>PMID:16636285</ref> <ref>PMID:24496152</ref> <ref>PMID:9003761</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
K2P potassium channels regulate cellular excitability using their selectivity filter (C-type) gate. C-type gating mechanisms, best characterized in homotetrameric potassium channels, remain controversial and are attributed to selectivity filter pinching, dilation, or subtle structural changes. The extent to which such mechanisms control C-type gating of innately heterodimeric K2Ps is unknown. Here, combining K2P2.1 (TREK-1) x-ray crystallography in different potassium concentrations, potassium anomalous scattering, molecular dynamics, and electrophysiology, we uncover unprecedented, asymmetric, potassium-dependent conformational changes that underlie K2P C-type gating. These asymmetric order-disorder transitions, enabled by the K2P heterodimeric architecture, encompass pinching and dilation, disrupt the S1 and S2 ion binding sites, require the uniquely long K2P SF2-M4 loop and conserved "M3 glutamate network," and are suppressed by the K2P C-type gate activator ML335. These findings demonstrate that two distinct C-type gating mechanisms can operate in one channel and underscore the SF2-M4 loop as a target for K2P channel modulator development. | |||
K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.,Lolicato M, Natale AM, Abderemane-Ali F, Crottes D, Capponi S, Duman R, Wagner A, Rosenberg JM, Grabe M, Minor DL Jr Sci Adv. 2020 Oct 30;6(44). pii: 6/44/eabc9174. doi: 10.1126/sciadv.abc9174., Print 2020 Oct. PMID:33127683<ref>PMID:33127683</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6w7b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Mus musculus]] | |||
[[Category: Lolicato M]] | [[Category: Lolicato M]] | ||
[[Category: Minor DL]] | [[Category: Minor DL]] | ||
Latest revision as of 17:17, 18 October 2023
K2P2.1 (TREK-1), 0 mM K+K2P2.1 (TREK-1), 0 mM K+
Structural highlights
FunctionKCNK2_MOUSE Ion channel that contributes to passive transmembrane potassium transport. Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner. In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2 (PubMed:24496152). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (PubMed:24496152).[1] [2] [3] [4] Publication Abstract from PubMedK2P potassium channels regulate cellular excitability using their selectivity filter (C-type) gate. C-type gating mechanisms, best characterized in homotetrameric potassium channels, remain controversial and are attributed to selectivity filter pinching, dilation, or subtle structural changes. The extent to which such mechanisms control C-type gating of innately heterodimeric K2Ps is unknown. Here, combining K2P2.1 (TREK-1) x-ray crystallography in different potassium concentrations, potassium anomalous scattering, molecular dynamics, and electrophysiology, we uncover unprecedented, asymmetric, potassium-dependent conformational changes that underlie K2P C-type gating. These asymmetric order-disorder transitions, enabled by the K2P heterodimeric architecture, encompass pinching and dilation, disrupt the S1 and S2 ion binding sites, require the uniquely long K2P SF2-M4 loop and conserved "M3 glutamate network," and are suppressed by the K2P C-type gate activator ML335. These findings demonstrate that two distinct C-type gating mechanisms can operate in one channel and underscore the SF2-M4 loop as a target for K2P channel modulator development. K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.,Lolicato M, Natale AM, Abderemane-Ali F, Crottes D, Capponi S, Duman R, Wagner A, Rosenberg JM, Grabe M, Minor DL Jr Sci Adv. 2020 Oct 30;6(44). pii: 6/44/eabc9174. doi: 10.1126/sciadv.abc9174., Print 2020 Oct. PMID:33127683[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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