8IXO

Intermediate structure of mPIEZO1-S2472E

8IXO の概要

• エントリーDOI: 10.2210/pdb8ixo/pdb
• EMDBエントリー: 35800 35994 36004
• 分子名称: Piezo-type mechanosensitive ion channel component 1, (9R,11S)-9-({[(1S)-1-HYDROXYHEXADECYL]OXY}METHYL)-2,2-DIMETHYL-5,7,10-TRIOXA-2LAMBDA~5~-AZA-6LAMBDA~5~-PHOSPHAOCTACOSANE-6,6,11-TRIOL, O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine, ... (4 entities in total)
• 機能のキーワード: open-state structure, piezo1 channel, membrane protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 888675.41

構造登録者

Liu, S.,Yang, X.,Chen, X.,Li, X.,Xiao, B. (登録日: 2023-04-01, 公開日: 2025-01-01, 最終更新日: 2025-03-05)

主引用文献

Liu, S.,Yang, X.,Chen, X.,Zhang, X.,Jiang, J.,Yuan, J.,Liu, W.,Wang, L.,Zhou, H.,Wu, K.,Tian, B.,Li, X.,Xiao, B.
An intermediate open structure reveals the gating transition of the mechanically activated PIEZO1 channel.
Neuron, 113:590-, 2025

PubMed Abstract: PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation. However, its distinct structural states remain undefined. Here, we employed an open-prone PIEZO1-S2472E mutant to capture an intermediate open structure. Compared with the curved and flattened structures of PIEZO1, the S2472E-Intermediate structure displays partially flattened blades, a downward and rotational motion of the top cap, and a spring-like compression of the linker connecting the cap to the pore-lining inner helix. These conformational changes open the cap gate and the hydrophobic transmembrane gate, whereas the intracellular lateral plug gate remains closed. The flattened structure of PIEZO1 with an up-state cap and closed cap gate might represent an inactivated state. Molecular dynamics (MD) simulations of ion conduction support the closed, intermediate open, and inactivated structural states. Mutagenesis and electrophysiological studies identified key domains and residues critical for the mechanical activation of PIEZO1. These studies collectively define the distinct structural states and gating transitions of PIEZO1.

PubMed: 39719701
DOI: 10.1016/j.neuron.2024.11.020

実験手法

ELECTRON MICROSCOPY (4 Å)