Structural Biology: Piezo Senses Tension through Curvature

Abstract

The sensations of sound, touch and pressure are mediated by mechanotransduction channels - transmembrane proteins whose ionic permeabilities are gated by mechanical forces. New structures of Piezo1 by cryoEM lead to the suggestion that this channel might sense membrane tension through changes in the local curvature of the membrane.

Figure 1.. Structure and possible gating mechanism of the Piezo1 channel.

(A) Top view of the cryoEM-derived structure of the homotrimeric Piezo1: the three colors denote the three subunits; the dashed arrows indicate the interlocking of the three polypeptide chains such that the outer domain is connected to the opposite inner domain; and the dashed black line and the black arrow indicate one of three ‘blades’. (B) Side view of Piezo1. CED in yellow denotes the carboxy-terminal extracellular domain, and CTD in purple denotes the carboxy-terminal domain. One of the three beam domains is labeled in black and indicated with an arrow. (A,B from PDB 6B3R.) (C) The curved blades of Piezo dimple the membrane into the cell (left panel). An increase in the membrane tension (σ) tends to flatten the dimple (right panel). As the dimple flattens, the angle (θ) between the beam and the flat membrane plane (beyond the channel) decreases (∆θ), and the projected area of the channel increases (∆a) when the channel shifts from a closed (solid arrow) to an open structure (dashed arrow). THU, transmembrane helical unit; IH, inner helix; OH, outer helix.