9czq
Ca2+ bound open-inactivated hSlo1 + beta2N-beta4 channel in detergent.
Structural highlights
FunctionB5BNX0_HUMAN KCMB4_HUMAN Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.[1] [2] [3] Publication Abstract from PubMedBK channels are large-conductance calcium (Ca(2+))-activated potassium channels crucial for neuronal excitability, muscle contraction, and neurotransmitter release. The pore-forming (alpha) subunits co-assemble with auxiliary (beta and gamma) subunits that modulate their function. Previous studies demonstrated that the N-termini of beta2-subunits can inactivate BK channels, but with no structural correlate. Here, we investigate BK beta2-subunit inactivation using cryo-electron microscopy, electrophysiology and molecular dynamics simulations. We find that the beta2 N-terminus occludes the pore only in the Ca(2+)-bound open state, via a ball-and-chain mechanism. The first three hydrophobic residues of beta2 are crucial for occlusion, while the remainder of the N-terminus remains flexible. Neither the closed channel conformation obtained in the absence of Ca(2+) nor an intermediate conformation found in the presence of Ca(2+) show density for the N-terminus of the beta2 subunit in their pore, likely due to narrower side access portals preventing their entry into the channel pore. Ball-and-chain inactivation of a human large conductance calcium-activated potassium channel.,Agarwal S, Kim ED, Lee S, Simon A, Accardi A, Nimigean CM Nat Commun. 2025 Feb 19;16(1):1769. doi: 10.1038/s41467-025-56844-4. PMID:39971906[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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