9EIO

Cryo-EM structure of the mutant KCa2.2_F244S channel

9EIO の概要

• エントリーDOI: 10.2210/pdb9eio/pdb
• EMDBエントリー: 48088
• 分子名称: Small conductance calcium-activated potassium channel protein 2, Calmodulin-1, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: ion channel, calmodulin binding protein. membrane protein, transport protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 229346.54

構造登録者

Nam, Y.W.,Zhang, M. (登録日: 2024-11-26, 公開日: 2025-04-23, 最終更新日: 2025-05-07)

主引用文献

Nam, Y.W.,Im, D.,Garcia, A.S.C.,Tringides, M.L.,Nguyen, H.M.,Liu, Y.,Orfali, R.,Ramanishka, A.,Pintilie, G.,Su, C.C.,Cui, M.,Logothetis, D.E.,Yu, E.W.,Wulff, H.,Chandy, K.G.,Zhang, M.
Cryo-EM structures of the small-conductance Ca 2+ -activated K Ca 2.2 channel.
Nat Commun, 16:3690-3690, 2025

PubMed Abstract: Small-conductance Ca-activated K (K2.1-K2.3) channels modulate neuronal and cardiac excitability. We report cryo-electron microscopy structures of the K2.2 channel in complex with calmodulin and Ca, alone or bound to two small molecule inhibitors, at 3.18, 3.50, 2.99 and 2.97 angstrom resolution, respectively. Extracellular S3-S4 loops in β-hairpin configuration form an outer canopy over the pore with an aromatic box at the canopy's center. Each S3-S4 β-hairpin is tethered to the selectivity filter in the neighboring subunit by inter-subunit hydrogen bonds. This hydrogen bond network flips the aromatic residue (Tyr362) in the filter's GYG signature by 180°, causing the outer selectivity filter to widen and water to enter the filter. Disruption of the tether by a mutation narrows the outer selectivity filter, realigns Tyr362 to the position seen in other K channels, and significantly increases unitary conductance. UCL1684, a mimetic of the bee venom peptide apamin, sits atop the canopy and occludes the opening in the aromatic box. AP14145, an analogue of a therapeutic for atrial fibrillation, binds in the central cavity below the selectivity filter and induces closure of the inner gate. These structures provide a basis for understanding the small unitary conductance and pharmacology of K2.x channels.

PubMed: 40246884
DOI: 10.1038/s41467-025-59061-1

実験手法

ELECTRON MICROSCOPY (3.62 Å)