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6w85

From Proteopedia

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K2P2.1 (TREK-1):ML335 complex, 200 mM K+

Structural highlights

6w85 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.8Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Patel AJ, Honore E, Lesage F, Fink M, Romey G, Lazdunski M. Inhalational anesthetics activate two-pore-domain background K+ channels. Nat Neurosci. 1999 May;2(5):422-6. PMID:10321245 doi:http://dx.doi.org/10.1038/8084
↑ Honore E, Patel AJ, Chemin J, Suchyna T, Sachs F. Desensitization of mechano-gated K2P channels. Proc Natl Acad Sci U S A. 2006 May 2;103(18):6859-64. Epub 2006 Apr 24. PMID:16636285 doi:http://dx.doi.org/10.1073/pnas.0600463103
↑ Hwang EM, Kim E, Yarishkin O, Woo DH, Han KS, Park N, Bae Y, Woo J, Kim D, Park M, Lee CJ, Park JY. A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nat Commun. 2014;5:3227. doi: 10.1038/ncomms4227. PMID:24496152 doi:http://dx.doi.org/10.1038/ncomms4227
↑ Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 1996 Dec 16;15(24):6854-62. PMID:9003761
↑ Lolicato M, Natale AM, Abderemane-Ali F, Crottès D, Capponi S, Duman R, Wagner A, Rosenberg JM, Grabe M, Minor DL Jr. K(2P) channel C-type gating involves asymmetric selectivity filter order-disorder transitions. Sci Adv. 2020 Oct 30;6(44):eabc9174. PMID:33127683 doi:10.1126/sciadv.abc9174

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6w85"

Categories: Large Structures | Mus musculus | Lolicato M | Minor DL

@@ Line 1: / Line 1: @@
 ==K2P2.1 (TREK-1):ML335 complex, 200 mM K+==
-<StructureSection load='6w85' size='340' side='right'caption='[[6w85]]' scene=''>
+<StructureSection load='6w85' size='340' side='right'caption='[[6w85]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W85 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6w85]] 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=6W85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W85 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=6w85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w85 OCA], [https://pdbe.org/6w85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w85 RCSB], [https://www.ebi.ac.uk/pdbsum/6w85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w85 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]] 3.8&#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=K:POTASSIUM+ION'>K</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=6w85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w85 OCA], [https://pdbe.org/6w85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w85 RCSB], [https://www.ebi.ac.uk/pdbsum/6w85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w85 ProSAT]</span></td></tr>
 </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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6w85" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Potassium channel 3D structures|Potassium channel 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
+[[Category: Mus musculus]]
 [[Category: Lolicato M]]
 [[Category: Minor DL]]

6w85

From Proteopedia

Current revision

K2P2.1 (TREK-1):ML335 complex, 200 mM K+

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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