Fig. 1

Topological and structural illustration of the designated mechanical and chemical activation of Piezo1. a, b A topological model (a) and structural model (based on the PDB 5Z10) (b) of Piezo1 showing the featured domains revealed from the reported cryo-EM structure of Piezo1³⁹, including the nine repetitive THUs, beam, anchor, and the C-terminal pore module comprising the OH, CED, IH, and CTD. The N-terminal THU1-THU3 were not structurally resolved. c Top view of the trimeric Piezo1 channel showing the three-bladed, propeller-like architecture and location of the L15-16 and L19-20 at the distal end of the blade. Key structural components involved in mechanical and chemical activation of Piezo1, including the extracellular loops of L15-16 and L19-20, beam, and L1342/L1345 (proposed to form the pivot of the beam), are labeled in a–c. As illustrated in steps (1)–(3), the blade-beam might form a designated transduction pathway for propagating action from the extracellular side of the distal blade to the central pore via utilizing the intracellular beam as a lever-like apparatus