7VNR

Structure of human KCNQ4-ML213 complex in digitonin

7VNR の概要

• エントリーDOI: 10.2210/pdb7vnr/pdb
• EMDBエントリー: 32046
• 分子名称: Potassium voltage-gated channel subfamily KQT member 4,Maltodextrin-binding protein, Calmodulin-3, (1S,2S,4R)-N-(2,4,6-trimethylphenyl)bicyclo[2.2.1]heptane-2-carboxamid, ... (4 entities in total)
• 機能のキーワード: kcnq4, ml213, cryo-em, digitonin, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 534722.49

構造登録者

Xu, F.,Zheng, Y. (登録日: 2021-10-11, 公開日: 2021-12-01, 最終更新日: 2024-06-19)

主引用文献

Zheng, Y.,Liu, H.,Chen, Y.,Dong, S.,Wang, F.,Wang, S.,Li, G.L.,Shu, Y.,Xu, F.
Structural insights into the lipid and ligand regulation of a human neuronal KCNQ channel.
Neuron, 110:237-, 2022

PubMed Abstract: The KCNQ family (KCNQ1-KCNQ5) of voltage-gated potassium channels plays critical roles in many physiological and pathological processes. It is known that the channel opening of all KCNQs relies on the signaling lipid molecule phosphatidylinositol 4,5-bisphosphate (PIP2). However, the molecular mechanism of PIP2 in modulating the opening of the four neuronal KCNQ channels (KCNQ2-KCNQ5), which are essential for regulating neuronal excitability, remains largely elusive. Here, we report the cryoelectron microscopy (cryo-EM) structures of human KCNQ4 determined in complex with the activator ML213 in the absence or presence of PIP2. Two PIP2 molecules are identified in the open-state structure of KCNQ4, which act as a bridge to couple the voltage-sensing domain (VSD) and pore domain (PD) of KCNQ4 leading to the channel opening. Our findings reveal the binding sites and activation mechanisms of ML213 and PIP2 for neuronal KCNQ channels, providing a framework for therapeutic intervention targeting on these important channels.

PubMed: 34767770
DOI: 10.1016/j.neuron.2021.10.029

実験手法

ELECTRON MICROSCOPY (2.8 Å)