Details

Autor(en) / Beteiligte

• Ge, Jingpeng
• Li, Wanqiu
• Zhao, Qiancheng
• Li, Ningning
• Chen, Maofei
• Zhi, Peng
• Li, Ruochong
• Gao, Ning
• Xiao, Bailong
• Yang, Maojun

Titel

Architecture of the mammalian mechanosensitive Piezo1 channel

Ist Teil von

• Nature (London), 2015-11, Vol.527 (7576), p.64-69

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2015

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• Piezo proteins are evolutionarily conserved and functionally diverse mechanosensitive cation channels. However, the overall structural architecture and gating mechanisms of Piezo channels have remained unknown. Here we determine the cryo-electron microscopy structure of the full-length (2,547 amino acids) mouse Piezo1 (Piezo1) at a resolution of 4.8 Å. Piezo1 forms a trimeric propeller-like structure (about 900 kilodalton), with the extracellular domains resembling three distal blades and a central cap. The transmembrane region has 14 apparently resolved segments per subunit. These segments form three peripheral wings and a central pore module that encloses a potential ion-conducting pore. The rather flexible extracellular blade domains are connected to the central intracellular domain by three long beam-like structures. This trimeric architecture suggests that Piezo1 may use its peripheral regions as force sensors to gate the central ion-conducting pore. Piezo1, a mechanosensitive cation channel, senses shear stress of blood flow for proper blood vessel development, regulates red blood cell function and controls cell migration and differentiation; here a trimeric architecture of this novel class of ion channel is reported, suggesting that Piezo1 may use its peripheral propeller-like ‘blades’ as force sensors to gate the central ion-conducting pore. Piezo1 channel architecture Mechanosensitive cation channels couple mechanical stimuli to various biological activities, including touch, hearing and blood pressure regulation, through a process termed 'mechanotransduction'. Piezo proteins have recently been identified as pore-forming subunits of mechanosensitive cation channels in metazoans, and Piezo1 senses shear stress of blood flow for proper blood vessel development, regulates red blood cell function, and controls cell migration and differentiation. These authors report a high-resolution cryo-electron microscopy structure of the full-length mouse Piezo1, which reveals the trimeric three-bladed propeller-like architecture of this membrane protein. They propose that Piezo1 may use its peripheral propeller-like 'blades' as force sensors to gate the central ion-conducting pore.