Journal Article

Structure and mechanogating mechanism of the Piezo1 channel

Wang, Jianhua, Wang, Jiawei, Geng, Jie, Zhou, Heng, Wu, Kun, Li, Xueming, Wang, Yanfeng, Xiao, Bailong, Chi, Shaopeng, Zhao, Qiancheng, Zhang, Tingxin, Liu, Wenhao, Dong, Meng-Qiu

2018

Overview

The mechanosensitive Piezo channels function as key eukaryotic mechanotransducers. However, their structures and mechanogating mechanisms remain unknown. Here we determine the three-bladed, propeller-like electron cryo-microscopy structure of mouse Piezo1 and functionally reveal its mechanotransduction components. Despite the lack of sequence repetition, we identify nine repetitive units consisting of four transmembrane helices each—which we term transmembrane helical units (THUs)—which assemble into a highly curved blade-like structure. The last transmembrane helix encloses a hydrophobic pore, followed by three intracellular fenestration sites and side portals that contain pore-property-determining residues. The central region forms a 90?Å-long intracellular beam-like structure, which undergoes a lever-like motion to connect THUs to the pore via the interfaces of the C-terminal domain, the anchor-resembling domain and the outer helix. Deleting extracellular loops in the distal THUs or mutating single residues in the beam impairs the mechanical activation of Piezo1. Overall, Piezo1 possesses a unique 38-transmembrane-helix topology and designated mechanotransduction components, which enable a lever-like mechanogating mechanism. The electron cryo-microscopy structure of full-length mouse Piezo1 reveals unique topological features such as the repetitive transmembrane helical units that constitute the highly curved transmembrane region, and identifies regions and single residues that are crucial for the mechanical activation of the channel. Structure and mechanism of ion channel Piezo1 Mechanosensitive cation channels convert external mechanical stimuli into various biological actions, including touch, hearing, balance and cardiovascular regulation. The eukaryotic Piezo proteins are mechanotransduction channels, although their structure and gating mechanisms are not well elucidated. In related papers in this issue of Nature , two groups report cryo-electron microscopy structures of the full-length mouse Piezo1 and reveal three flexible propeller blades. Each blade is made up of at least 26 helices, forming a series of helical bundles, which adopt a curved transmembrane region. A kinked beam and anchor domain link these Piezo repeats to the pore, giving clues as to how the channel responds to membrane tension and mechanical force.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 101/28 / 14 / 631/378/2586 / 631/535/1258/1259 / 82 / 82/80 / 82/83 / 9/74 / Data collection / Helices / Humanities and Social Sciences / Hydrophobicity / Interfaces / Intracellular / Ion channels / Mechanotransduction / Microscopy / multidisciplinary / Observations / Physiological aspects / Protein structure / Proteins / Residues / Science / Topology