9CZO

Ca2+ bound intermediate state of hSlo1 + beta2N-beta4 channel in nanodisc.

9CZO の概要

• エントリーDOI: 10.2210/pdb9czo/pdb
• EMDBエントリー: 46423
• 分子名称: Isoform 5 of Calcium-activated potassium channel subunit alpha-1, Large-conductance Ca2+-activated K+ channel beta2 subunit,Calcium-activated potassium channel subunit beta-4, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: potassium ion channel, calcium and voltage gated ion channel, big potassium channel, human bk, hslo1, intermediate hslo1, ball and chain inactivation, hslo1 inactivating subunit complex, nanodisc, membrane protein, beta2, beta4
• 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: 594443.72

構造登録者

Agarwal, S.,Nimigean, C. (登録日: 2024-08-05, 公開日: 2025-03-05)

主引用文献

Agarwal, S.,Kim, E.D.,Lee, S.,Simon, A.,Accardi, A.,Nimigean, C.M.
Ball-and-chain inactivation of a human large conductance calcium-activated potassium channel.
Nat Commun, 16:1769-1769, 2025

PubMed Abstract: BK channels are large-conductance calcium (Ca)-activated potassium channels crucial for neuronal excitability, muscle contraction, and neurotransmitter release. The pore-forming (α) subunits co-assemble with auxiliary (β and γ) subunits that modulate their function. Previous studies demonstrated that the N-termini of β2-subunits can inactivate BK channels, but with no structural correlate. Here, we investigate BK β2-subunit inactivation using cryo-electron microscopy, electrophysiology and molecular dynamics simulations. We find that the β2 N-terminus occludes the pore only in the Ca-bound open state, via a ball-and-chain mechanism. The first three hydrophobic residues of β2 are crucial for occlusion, while the remainder of the N-terminus remains flexible. Neither the closed channel conformation obtained in the absence of Ca nor an intermediate conformation found in the presence of Ca show density for the N-terminus of the β2 subunit in their pore, likely due to narrower side access portals preventing their entry into the channel pore.

PubMed: 39971906
DOI: 10.1038/s41467-025-56844-4

実験手法

ELECTRON MICROSCOPY (2.87 Å)