6b3r | pdb_00006b3r
Structure of the mechanosensitive channel Piezo1
Structural highlights
Function[PIEZ1_MOUSE] Pore-forming subunit of a mechanosensitive non-specific cation channel. Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium. Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling. In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation. Plays a key role in blood vessel formation and vascular structure in both development and adult physiology.[1] [2] [3] [4] [5] Publication Abstract from PubMedMechanosensitive ion channels convert external mechanical stimuli into electrochemical signals for critical processes including touch sensation, balance, and cardiovascular regulation. The best understood mechanosensitive channel, MscL, opens a wide pore, which accounts for mechanosensitive gating due to in-plane area expansion. Eukaryotic Piezo channels have a narrow pore and therefore must capture mechanical forces to control gating in another way. We present a cryo-EM structure of mouse Piezo1 in a closed conformation at 3.7A-resolution. The channel is a triskelion with arms consisting of repeated arrays of 4-TM structural units surrounding a pore. Its shape deforms the membrane locally into a dome. We present a hypothesis in which the membrane deformation changes upon channel opening. Quantitatively, membrane tension will alter gating energetics in proportion to the change in projected area under the dome. This mechanism can account for highly sensitive mechanical gating in the setting of a narrow, cation-selective pore. Structure-based membrane dome mechanism for Piezo mechanosensitivity.,Guo YR, MacKinnon R Elife. 2017 Dec 12;6. pii: 33660. doi: 10.7554/eLife.33660. PMID:29231809[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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