9ZRR

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

This is a non-PDB format compatible entry.

Summary for 9ZRR

• Entry DOI: 10.2210/pdb9zrr/pdb
• EMDB information: 74628
• Descriptor: Small conductance calcium-activated potassium channel protein 2, Calmodulin-1, POTASSIUM ION, ... (6 entities in total)
• Functional Keywords: intermediate conductance calcium-activated potassium channel, ion channel, calmodulin binding protein, transport protein, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 231270.93

Authors

Nam, Y.W.,Ramanishka, A.,Zhang, M. (deposition date: 2025-12-20, release date: 2026-05-27)

Primary citation

Ramanishka, A.,Nasburg, J.A.,Xu, Y.,Ma, X.,Mehvar, R.,Cui, M.,Nam, Y.W.,Wulff, H.,Zhang, M.
Structural basis for the subtype-selective activation of K Ca 3.1 channels.
Structure, 2026

PubMed Abstract: The intermediate-conductance (K3.1) and the small-conductance (K2.2) Ca-activated K channels share a Ca-calmodulin dependent gating mechanism. We report cryo-electron microscopy structures of K3.1 and K2.2 in complex with two benzothiazole-type activators. While SKA-31 is only moderately selective (∼7.3-fold), its derivative SKA-111 exhibits ∼70-fold selectivity for K3.1 over K2.2. SKA-31 and SKA-111 both bind in a pocket at the interface between the SA 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 K3.1 over K2.2. In the K3.1 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 K3.1 than in K2.2. The resulting higher binding energy explains the improved selectivity of SKA-111 for K3.1 compared to the less selective SKA-31.

PubMed: 42140186
DOI: 10.1016/j.str.2026.04.010

Experimental method

ELECTRON MICROSCOPY (3.31 Å)