7PXE

Ca2+ bound Drosophila Slo channel

7PXE の概要

• エントリーDOI: 10.2210/pdb7pxe/pdb
• EMDBエントリー: 13700
• 分子名称: Isoform J of Calcium-activated potassium channel slowpoke, CALCIUM ION, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: potassium transport, bk channel, transport protein
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 538006.83

構造登録者

Raisch, T.,Brockmann, A.,Ebbinghaus-Kintscher, U.,Freigang, J.,Gutbrod, O.,Kubicek, J.,Maertens, B.,Hofnagel, O.,Raunser, S. (登録日: 2021-10-08, 公開日: 2021-12-15, 最終更新日: 2024-07-17)

主引用文献

Raisch, T.,Brockmann, A.,Ebbinghaus-Kintscher, U.,Freigang, J.,Gutbrod, O.,Kubicek, J.,Maertens, B.,Hofnagel, O.,Raunser, S.
Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM.
Nat Commun, 12:7164-7164, 2021

PubMed Abstract: 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.

PubMed: 34887422
DOI: 10.1038/s41467-021-27435-w

実験手法

ELECTRON MICROSCOPY (2.38 Å)