9zrr

Cryo-EM structure of KCa2.2/calmodulin channel in complex with SKA111.

spinqualitylabelsall models 9zrr, resolution 3.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9zrr 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 3.31Å Ligands: A1C3U, CA, K Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KCNN2_HUMAN Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin. Publication Abstract from PubMed The intermediate-conductance (K(Ca)3.1) and the small-conductance (K(Ca)2.2) Ca(2+)-activated K(+) channels share a Ca(2+)-calmodulin dependent gating mechanism. We report cryo-electron microscopy structures of K(Ca)3.1 and K(Ca)2.2 in complex with two benzothiazole-type activators. While SKA-31 is only moderately selective ( approximately 7.3-fold), its derivative SKA-111 exhibits approximately 70-fold selectivity for K(Ca)3.1 over K(Ca)2.2. SKA-31 and SKA-111 both bind in a pocket at the interface between the S(45)A helix and calmodulin where they allosterically modulate the inner gate of the two channels. SKA-31 binds with comparable energies in the two channels, consistent with its moderate selectivity for K(Ca)3.1 over K(Ca)2.2. In the K(Ca)3.1 structure, the calmodulin helix IV is positioned outward, forming a pocket that more readily accommodates the bulkier SKA-111 that sits deeper inside calmodulin's N-lobe in K(Ca)3.1 than in K(Ca)2.2. The resulting higher binding energy explains the improved selectivity of SKA-111 for K(Ca)3.1 compared to the less selective SKA-31. Structural basis for the subtype-selective activation of K(Ca)3.1 channels.,Ramanishka A, Nasburg JA, Xu Y, Ma X, Mehvar R, Cui M, Nam YW, Wulff H, Zhang M Structure. 2026 May 14:S0969-2126(26)00116-4. doi: 10.1016/j.str.2026.04.010. PMID:42140186 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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