9VUA

channel A complex with 1

Summary for 9VUA

• Entry DOI: 10.2210/pdb9vua/pdb
• EMDB information: 65357
• Descriptor: Calmodulin-1, Small conductance calcium-activated potassium channel protein 2, Apamin, ... (5 entities in total)
• Functional Keywords: channel a complex with 1, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 311157.11

Authors

Jiang, D.H.,Ma, B. (deposition date: 2025-07-12, release date: 2026-03-11)

Primary citation

Ma, B.,Wu, D.,Cao, E.,Chi, C.,Wang, Z.,Xia, Z.,Sun, L.H.,Pan, B.,Jiang, D.,Zhang, W.
Structural mechanisms for inhibition and activation of human small-conductance Ca 2+ -activated potassium channel SK2.
Nat Commun, 17:1770-1770, 2026

PubMed Abstract: The small-conductance calcium-activated potassium (SK1-3 or K2) 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.

PubMed: 41540047
DOI: 10.1038/s41467-026-68475-4

Experimental method

ELECTRON MICROSCOPY (3.23 Å)