7pxh: Difference between revisions
New page: '''Unreleased structure''' The entry 7pxh is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Emodepside-bound Drosophila Slo channel== | |||
<StructureSection load='7pxh' size='340' side='right'caption='[[7pxh]], [[Resolution|resolution]] 2.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7pxh]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PXH FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6PL:(4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM+4-OXIDE'>6PL</scene>, <scene name='pdbligand=8I2:(3~{S},6~{R},9~{S},12~{R},15~{S},18~{R},21~{S},24~{R})-4,6,10,16,18,22-hexamethyl-3,9,15,21-tetrakis(2-methylpropyl)-12,24-bis[(4-morpholin-4-ylphenyl)methyl]-1,7,13,19-tetraoxa-4,10,16,22-tetrazacyclotetracosane-2,5,8,11,14,17,20,23-octone'>8I2</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7pxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pxh OCA], [https://pdbe.org/7pxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pxh RCSB], [https://www.ebi.ac.uk/pdbsum/7pxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pxh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[https://www.uniprot.org/uniprot/SLO_DROME SLO_DROME]] Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Kinetics are determined by alternative splicing, phosphorylation status and its combination interaction with Slob and 14-3-3-zeta. While the interaction with Slob1 alone increases its activity, its interaction with both Slob1 and 14-3-3-zeta decreases its activity.<ref>PMID:1497890</ref> <ref>PMID:1857984</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Slowpoke (Slo) potassium channels display extraordinarily high conductance, are synergistically activated by a positive transmembrane potential and high intracellular Ca(2+) concentrations and are important targets for insecticides and antiparasitic drugs. However, it is unknown how these compounds modulate ion translocation and whether there are insect-specific binding pockets. Here, we report structures of Drosophila Slo in the Ca(2+)-bound and Ca(2+)-free form and in complex with the fungal neurotoxin verruculogen and the anthelmintic drug emodepside. Whereas the architecture and gating mechanism of Slo channels are conserved, potential insect-specific binding pockets exist. Verruculogen inhibits K(+) transport by blocking the Ca(2+)-induced activation signal and precludes K(+) from entering the selectivity filter. Emodepside decreases the conductance by suboptimal K(+) coordination and uncouples ion gating from Ca(2+) and voltage sensing. Our results expand the mechanistic understanding of Slo regulation and lay the foundation for the rational design of regulators of Slo and other voltage-gated ion channels. | |||
Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM.,Raisch T, Brockmann A, Ebbinghaus-Kintscher U, Freigang J, Gutbrod O, Kubicek J, Maertens B, Hofnagel O, Raunser S Nat Commun. 2021 Dec 9;12(1):7164. doi: 10.1038/s41467-021-27435-w. PMID:34887422<ref>PMID:34887422</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7pxh" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Brockmann, A]] | |||
[[Category: Ebbinghaus-Kintscher, U]] | |||
[[Category: Freigang, J]] | |||
[[Category: Gutbrod, O]] | |||
[[Category: Hofnagel, O]] | |||
[[Category: Kubicek, J]] | |||
[[Category: Maertens, B]] | |||
[[Category: Raisch, T]] | |||
[[Category: Raunser, S]] | |||
[[Category: Bk channel]] | |||
[[Category: Potassium transport]] | |||
[[Category: Transport protein]] | |||
Latest revision as of 18:41, 22 December 2021
Emodepside-bound Drosophila Slo channelEmodepside-bound Drosophila Slo channel
Structural highlights
Function[SLO_DROME] Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Kinetics are determined by alternative splicing, phosphorylation status and its combination interaction with Slob and 14-3-3-zeta. While the interaction with Slob1 alone increases its activity, its interaction with both Slob1 and 14-3-3-zeta decreases its activity.[1] [2] Publication Abstract from PubMedSlowpoke (Slo) potassium channels display extraordinarily high conductance, are synergistically activated by a positive transmembrane potential and high intracellular Ca(2+) concentrations and are important targets for insecticides and antiparasitic drugs. However, it is unknown how these compounds modulate ion translocation and whether there are insect-specific binding pockets. Here, we report structures of Drosophila Slo in the Ca(2+)-bound and Ca(2+)-free form and in complex with the fungal neurotoxin verruculogen and the anthelmintic drug emodepside. Whereas the architecture and gating mechanism of Slo channels are conserved, potential insect-specific binding pockets exist. Verruculogen inhibits K(+) transport by blocking the Ca(2+)-induced activation signal and precludes K(+) from entering the selectivity filter. Emodepside decreases the conductance by suboptimal K(+) coordination and uncouples ion gating from Ca(2+) and voltage sensing. Our results expand the mechanistic understanding of Slo regulation and lay the foundation for the rational design of regulators of Slo and other voltage-gated ion channels. Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM.,Raisch T, Brockmann A, Ebbinghaus-Kintscher U, Freigang J, Gutbrod O, Kubicek J, Maertens B, Hofnagel O, Raunser S Nat Commun. 2021 Dec 9;12(1):7164. doi: 10.1038/s41467-021-27435-w. PMID:34887422[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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