9CZJ

Ca2+ free hSlo1 + beta2N-beta4 channel in detergent.

Summary for 9CZJ

• Entry DOI: 10.2210/pdb9czj/pdb
• EMDB information: 46418
• Descriptor: 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, CHOLESTEROL, ... (4 entities in total)
• Functional Keywords: potassium ion channel, calcium and voltage gated ion channel, big potassium channel, human bk, hslo1, apo hslo1, closed hslo1, ball and chain inactivation, hslo1 inactivating subunit complex, detergent micelle, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 587191.59

Authors

Agarwal, S.,Nimigean, C. (deposition date: 2024-08-05, release date: 2025-03-05)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.54 Å)