9L8W

Human KCNQ2-CaM in complex with QO-58

This is a non-PDB format compatible entry.

Summary for 9L8W

• Entry DOI: 10.2210/pdb9l8w/pdb
• EMDB information: 62892
• Descriptor: Potassium voltage-gated channel subfamily KQT member 2, QO-58 (2 entities in total)
• Functional Keywords: kcnq2, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 387452.42

Authors

Zhao, Y.W.,Yang, Z.N.,Du, X.N.,Guo, J.T. (deposition date: 2024-12-28, release date: 2026-01-21)

Primary citation

Zhao, Y.,Yang, Z.,Shi, S.,Hao, H.,Li, X.,Ma, D.,Su, N.,Zhao, W.,Shao, J.,An, Y.,Wang, K.,Liu, Y.,Zou, L.,Qi, J.,Zhang, H.,Guo, J.,Du, X.
Structure basis for the activation of KCNQ2 by endogenous and exogenous ligands.
Cell Rep, 45:116771-116771, 2025

PubMed Abstract: The voltage-gated potassium channel KCNQ2 is crucial for stabilizing neuronal membrane potential, and its mutations can cause various epilepsies. KCNQ2 is activated by endogenous ligand phosphatidylinositol-4,5-bisphosphate (PIP) and exogenous ligands, yet the structural mechanisms underlying these activations remain unclear. Here, we report the cryo-electron microscopy structures of human KCNQ2 in complex with exogenous ligands QO-58 and QO-83 in the absence or presence of PIP in either closed or open conformation. While QO-83 binds in the classical fenestration pocket of the pore domain, QO-58 mainly binds at the flank of S4 in the voltage-sensing domain. These structures, along with electrophysiological assays and computational studies, provide mechanistic insights into the ligand activation of KCNQ2 and may guide the development of anti-epileptic drugs targeting KCNQ2.

PubMed: 41442279
DOI: 10.1016/j.celrep.2025.116771

Experimental method

ELECTRON MICROSCOPY (2.9 Å)