9MY3

Structure of Xenopus KCNQ1-CaM in GDN

Summary for 9MY3

• Entry DOI: 10.2210/pdb9my3/pdb
• EMDB information: 48725
• Descriptor: Potassium voltage-gated channel subfamily KQT member 1, Calmodulin-1 (2 entities in total)
• Functional Keywords: potassium ion channel protein, transport protein
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 8
• Total formula weight: 316910.73

Authors

Kyriakis, E.,Russo, S.,Molinarolo, S.,Eldstrom, J.,Van Petegem, F.,Fedida, D. (deposition date: 2025-01-21, release date: 2025-10-15)

Primary citation

Kyriakis, E.,Sastre, D.,Eldstrom, J.,Roscioni, A.,Russo, S.,Ataei, F.,Dou, Y.,Chan, M.,Molinarolo, S.,Maragliano, L.,Van Petegem, F.,Fedida, D.
A physiologically-relevant intermediate state structure of a voltage-gated potassium channel.
Nat Commun, 16:8814-8814, 2025

PubMed Abstract: Voltage-gated potassium ion (K) channels perform critical roles in many physiological processes, while gain- or loss-of-function mutations lead to life-threatening pathologies. Here, we establish the high-resolution structure of a pivotal intermediate state of the Kv7.1 (KCNQ1) channel using cryogenic electron microscopy. The 3.53 Å resolution structure reveals straightened upper S1 and S2 voltage sensor helices, distancing them from the pore filter helix compared to fully activated channels. The outward translation of the S4 voltage sensor is essentially complete in this intermediate state, and the S4-S6 helices and the S4-S5 linker do not change position significantly between intermediate and activated states. The PIP2 ligand can bind in both states. Movement of S1 and S2 helices towards the filter helix from intermediate to activated states may explain smaller components of KCNQ1 voltage sensor fluorescence, differential Rb/K selectivity, and pharmacological responses to activators and inhibitors. Single channel recordings and the location of long QT mutations suggest the potential physiological and disease importance of the intermediate state.

PubMed: 41044058
DOI: 10.1038/s41467-025-64060-3

Experimental method

ELECTRON MICROSCOPY (3.46 Å)