9vub
channel C complex with 3
Structural highlights
FunctionKCNN2_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 PubMedThe small-conductance calcium-activated potassium (SK1-3 or K(Ca)2) channels regulate the intrinsic excitability and firing frequency of excitable cells. SK channels are modulated by a variety of distinct modulators; however, the underlying mechanisms remain elusive. Here, we present four cryoelectron microscopy structures of the human SK2-calmodulin complex bound with apamin, UCL1684, AP30663, and CAD-1883, elucidating their distinct binding sites and regulatory mechanisms. Apamin and UCL1684 compete for a similar binding site above the selectivity filter, which is formed by the distinct S3-S4 linker of SK2. CAD-1883 glues the N-lobe of calmodulin and the S4-S5 linker of SK2, reinforcing the open state. In contrast, AP30663 resides in the central cavity of SK2, blocking ion conductance. This study reveals multiple modulation sites in SK2 and the molecular mechanisms for the inhibition and potentiation of SK channels, which could advance rational drug design targeting SK2 channel for the treatment of cardiovascular and neurological disorders. Structural mechanisms for inhibition and activation of human small-conductance Ca(2+)-activated potassium channel SK2.,Ma B, Wu D, Cao E, Chi C, Wang Z, Xia Z, Sun LH, Pan B, Jiang D, Zhang W Nat Commun. 2026 Jan 15;17(1):1770. doi: 10.1038/s41467-026-68475-4. PMID:41540047[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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