View source for 6w86


==K2P2.1 (TREK-1):ML335 complex, 100 mM K+==
<StructureSection load='6w86' size='340' side='right'caption='[[6w86]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W86 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]] 3.299&#8491;</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=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LNK:PENTANE'>LNK</scene>, <scene name='pdbligand=OCT:N-OCTANE'>OCT</scene>, <scene name='pdbligand=Q6F:N-[(2,4-dichlorophenyl)methyl]-4-[(methylsulfonyl)amino]benzamide'>Q6F</scene>, <scene name='pdbligand=R16:HEXADECANE'>R16</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=6w86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w86 OCA], [https://pdbe.org/6w86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w86 RCSB], [https://www.ebi.ac.uk/pdbsum/6w86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w86 ProSAT]</span></td></tr>
</table>
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6w86" style="background-color:#fffaf0;"></div>

==See Also==
*[[Potassium channel 3D structures|Potassium channel 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lolicato M]]
[[Category: Minor DL]]