7WLT

the Curved Structure of mPIEZO1 in Lipid Bilayer

7WLT の概要

• エントリーDOI: 10.2210/pdb7wlt/pdb
• EMDBエントリー: 32592
• 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, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, ... (4 entities in total)
• 機能のキーワード: force, flexible, complex, 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: 897680.07

構造登録者

Yang, X.,Lin, C.,Chen, X.,Li, S.,Li, X.,Xiao, B. (登録日: 2022-01-13, 公開日: 2022-04-13, 最終更新日: 2022-07-06)

主引用文献

Yang, X.,Lin, C.,Chen, X.,Li, S.,Li, X.,Xiao, B.
Structure deformation and curvature sensing of PIEZO1 in lipid membranes.
Nature, 604:377-383, 2022

PubMed Abstract: PIEZO channels respond to piconewton-scale forces to mediate critical physiological and pathophysiological processes. Detergent-solubilized PIEZO channels form bowl-shaped trimers comprising a central ion-conducting pore with an extracellular cap and three curved and non-planar blades with intracellular beams, which may undergo force-induced deformation within lipid membranes. However, the structures and mechanisms underlying the gating dynamics of PIEZO channels in lipid membranes remain unresolved. Here we determine the curved and flattened structures of PIEZO1 reconstituted in liposome vesicles, directly visualizing the substantial deformability of the PIEZO1-lipid bilayer system and an in-plane areal expansion of approximately 300 nm in the flattened structure. The curved structure of PIEZO1 resembles the structure determined from detergent micelles, but has numerous bound phospholipids. By contrast, the flattened structure exhibits membrane tension-induced flattening of the blade, bending of the beam and detaching and rotating of the cap, which could collectively lead to gating of the ion-conducting pathway. On the basis of the measured in-plane membrane area expansion and stiffness constant of PIEZO1 (ref. ), we calculate a half maximal activation tension of about 1.9 pN nm, matching experimentally measured values. Thus, our studies provide a fundamental understanding of how the notable deformability and structural rearrangement of PIEZO1 achieve exquisite mechanosensitivity and unique curvature-based gating in lipid membranes.

PubMed: 35388220
DOI: 10.1038/s41586-022-04574-8

実験手法

ELECTRON MICROSCOPY (3.46 Å)