The Structural Basis for Sensing bythe Piezo1 Protein.

Abstract

Mechanotransduction is one of the processes by which cells sense and convert mechanical stimuli into biological signals. Experimental data from various species have revealed crucial roles for mechanotransduction in organ development and a plethora of physiological activities. Piezo proteins have recently been identified as the long-sought-after mechanically activated cation channels in eukaryotes. The architecture of mouse Piezo1 (mPiezo1) channel determined by cryoelectron microscopicsingle-particle analysis at medium resolution yielded important insights into the mechanical force sensing mechanism. mPiezo1 is found to form a trimeric propeller-like structure with the extracellular domains resembling three distal blades and a central cap. The transmembrane region consists of a central pore module that likely determines the ion-conducting properties of mPiezo1, and three peripheral wings formed by arrays of paired transmembrane helices. Compared with the central pore module, the three distal blades display considerably larger flexibility. In the intracellular region, three long beam-like domains (∼80Å in length) support the whole transmembrane region and connect the mobile peripheral regions to the central pore module. This unique design suggests that the trimeric mPiezo1 may mechanistically function in similar principles as how propellers sense and transduce force to control the ion conductivity. This review summarizes the current knowledge on the structure and proposes possible gating mechanisms of mPiezo1.