| First Author | Zhao Q | Year | 2018 |
| Journal | Nature | Volume | 554 |
| Issue | 7693 | Pages | 487-492 |
| PubMed ID | 29469092 | Mgi Jnum | J:273510 |
| Mgi Id | MGI:6294163 | Doi | 10.1038/nature25743 |
| Citation | Zhao Q, et al. (2018) Structure and mechanogating mechanism of the Piezo1 channel. Nature 554(7693):487-492 |
| abstractText | 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 A-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. |
