6Q6C

Pore-modulating toxins exploit inherent slow inactivation to block K+ channels

6Q6C の概要

• エントリーDOI: 10.2210/pdb6q6c/pdb
• 分子名称: Kunitz-type conkunitzin-S1, PHOSPHATE ION, NITRATE ION, ... (5 entities in total)
• 機能のキーワード: toxin
• 由来する生物種: Conus striatus (Striated cone)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14571.35

構造登録者

Karbat, I.,Gueta, H.,Fine, S.,Szanto, T.,Hamer-Rogotner, S.,Dym, O.,Frolow, F.,Gordon, D.,Panyi, G.,Gurevitz, M.,Reuveny, E. (登録日: 2018-12-10, 公開日: 2019-08-21, 最終更新日: 2024-11-13)

主引用文献

Karbat, I.,Altman-Gueta, H.,Fine, S.,Szanto, T.,Hamer-Rogotner, S.,Dym, O.,Frolow, F.,Gordon, D.,Panyi, G.,Gurevitz, M.,Reuveny, E.
Pore-modulating toxins exploit inherent slow inactivation to block K+channels.
Proc.Natl.Acad.Sci.USA, 116:18700-18709, 2019

PubMed Abstract: Voltage-dependent potassium channels (Ks) gate in response to changes in electrical membrane potential by coupling a voltage-sensing module with a K-selective pore. Animal toxins targeting Ks are classified as pore blockers, which physically plug the ion conduction pathway, or as gating modifiers, which disrupt voltage sensor movements. A third group of toxins blocks K conduction by an unknown mechanism via binding to the channel turrets. Here, we show that Conkunitzin-S1 (Cs1), a peptide toxin isolated from cone snail venom, binds at the turrets of K1.2 and targets a network of hydrogen bonds that govern water access to the peripheral cavities that surround the central pore. The resulting ectopic water flow triggers an asymmetric collapse of the pore by a process resembling that of inherent slow inactivation. Pore modulation by animal toxins exposes the peripheral cavity of K channels as a novel pharmacological target and provides a rational framework for drug design.

PubMed: 31444298
DOI: 10.1073/pnas.1908903116

実験手法

X-RAY DIFFRACTION (1.3 Å)