9O5O

Cryo-EM structure of the human SK2-4 chimera/calmodulin channel complex bound to a small molecule activator

これはPDB形式変換不可エントリーです。

9O5O の概要

• エントリーDOI: 10.2210/pdb9o5o/pdb
• 関連するPDBエントリー: 9O48
• EMDBエントリー: 70145
• 分子名称: Intermediate conductance calcium-activated potassium channel protein 4,Small conductance calcium-activated potassium channel protein 2 chimera, Calmodulin-1, N-(2,1,3-benzoxadiazol-4-yl)-4-(trifluoromethyl)benzamide, ... (5 entities in total)
• 機能のキーワード: ion channel, potassium, activator, calmodulin, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 266887.19

構造登録者

Cassell, S.J.,Khoshouei, M.,Wilhelm, W.A.,Whicher, J.R. (登録日: 2025-04-10, 公開日: 2025-07-09, 最終更新日: 2025-12-17)

主引用文献

Cassell, S.J.,Li, W.,Krautwald, S.,Khoshouei, M.,Lee, Y.T.,Hou, J.,Guan, W.,Peukert, S.,Weihofen, W.,Whicher, J.R.
Mechanism of SK2 channel gating and its modulation by the bee toxin apamin and small molecules.
Elife, 14:-, 2025

PubMed Abstract: Small-conductance calcium-activated potassium channel 2 (SK2) serves a variety of biological functions by coupling intracellular calcium dynamics with membrane potential. SK2 modulators are in development for the treatment of neurological and cardiovascular diseases, though the mechanisms of pharmacological modulation remain incompletely understood. We determined structures of an SK2-4 chimeric channel in Ca-bound and Ca-free conformations and in complex with the bee toxin apamin, a small molecule inhibitor, and a small molecule activator. The structures revealed that the S3-S4 linker forms a hydrophobic constriction at the extracellular opening of the pore. Apamin binds to this extracellular constriction and blocks the exit of potassium ions. Furthermore, we identified a structurally related SK2 inhibitor and activator that bind to the transmembrane domains. The compounds exert opposing effects on gating by differentially modulating the conformation of the S6 helices. These results provide important mechanistic insights to facilitate the development of targeted SK2 channel therapeutics.

PubMed: 41342453
DOI: 10.7554/eLife.107733

実験手法

ELECTRON MICROSCOPY (3.1 Å)