10AD

Cryo-EM structure of the human BK channel bound to the agonist NS1619

これはPDB形式変換不可エントリーです。

10AD の概要

• エントリーDOI: 10.2210/pdb10ad/pdb
• EMDBエントリー: 75024
• 分子名称: Isoform 5 of Calcium-activated potassium channel subunit alpha-1, MAGNESIUM ION, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: bk, slo1, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 503241.66

構造登録者

Gonzalez-Sanabria, N.,Contreras, G.F.,Perozo, E.,Latorre, R. (登録日: 2026-01-08, 公開日: 2026-02-04, 最終更新日: 2026-02-11)

主引用文献

Gonzalez-Sanabria, N.,Contreras, G.F.,Rojas, M.,Duarte, Y.,Gonzalez-Nilo, F.D.,Perozo, E.,Latorre, R.
The BK channel-NS1619 agonist complex reveals molecular insights into allosteric activation gating.
Proc.Natl.Acad.Sci.USA, 123:e2507707123-e2507707123, 2026

PubMed Abstract: BK channels play essential roles in a wealth of physiological functions, including regulating smooth muscle tone and neurotransmitter release. Its dysfunction, often caused by loss-of-function mutations, can lead to severe phenotypes, including ataxia and sensory impairment. Despite the therapeutic potential of BK channel agonists, the molecular mechanisms by which they stabilize the pore's open conformation remain unclear. Using cryoelectron microscopy and molecular dynamic simulations, we identified that NS1619, a synthetic benzimidazolone agonist, first described as a BK opener, binds within a pocket formed by the S6/RCK1 linker and the S4 transmembrane segment. Our simulations suggest that agonist binding promotes a twisting motion in the S6 segment, enabling critical interactions with residues K330, K331, and F223. These findings provide a molecular model for the mechanism of NS1619 and suggest that its binding site can accommodate other agonists, highlighting a promising target for therapeutic development.

PubMed: 41591909
DOI: 10.1073/pnas.2507707123

実験手法

ELECTRON MICROSCOPY (3.44 Å)