9d19

Ca2+ bound open-inactivated hSlo1 + beta2N-beta4 channel in detergent-conformation 3 of inactivating domain

spinqualitylabelsall models 9d19, resolution 2.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9d19 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.88Å Ligands: CA, CLR, K, MG, POV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KCMA1_HUMAN Publication Abstract from PubMed BK 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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