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-Structure paper
タイトル | Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 7164, Year 2021 |
掲載日 | 2021年12月9日 |
著者 | Tobias Raisch / Andreas Brockmann / Ulrich Ebbinghaus-Kintscher / Jörg Freigang / Oliver Gutbrod / Jan Kubicek / Barbara Maertens / Oliver Hofnagel / Stefan Raunser / |
PubMed 要旨 | Slowpoke (Slo) potassium channels display extraordinarily high conductance, are synergistically activated by a positive transmembrane potential and high intracellular Ca concentrations and are ...Slowpoke (Slo) potassium channels display extraordinarily high conductance, are synergistically activated by a positive transmembrane potential and high intracellular Ca 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-bound and Ca-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-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 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. |
リンク | Nat Commun / PubMed:34887422 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.38 - 2.73 Å |
構造データ | EMDB-13700, PDB-7pxe: EMDB-13701, PDB-7pxf: EMDB-13702, PDB-7pxg: EMDB-13703, PDB-7pxh: |
化合物 | ChemComp-CA: ChemComp-MG: ChemComp-6PL: ChemComp-CLR: ChemComp-K: ChemComp-HOH: ChemComp-8H5: ChemComp-8I2: |
由来 |
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キーワード | TRANSPORT PROTEIN (運搬体タンパク質) / Potassium transport / BK channel |