6bpz
From Proteopedia
Structure of the mechanically activated ion channel Piezo1
Structural highlights
FunctionPIEZ1_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 PubMedPiezo1 and Piezo2 are mechanically activated ion channels that mediate touch perception, proprioception and vascular development. Piezos are distinct from other ion channels and their structure remains poorly defined, impeding detailed study of their gating and ion permeation properties. Here we report a high-resolution cryo-electron microscopy structure of the mouse Piezo1 trimer. The detergent-solubilized complex adopts a three-blade propeller shape with a curved transmembrane region containing at least 26 transmembrane helices per protomer. The flexible propeller blades can adopt distinct conformations, and consist of a series of four-transmembrane helix bundles we term 'Piezo repeats'. Carboxy-terminal domains line the central ion pore, and the channel is closed by constrictions in the cytosol. A kinked helical beam and anchor domain link the Piezo repeats to the pore, and are poised to control gating allosterically. The structure provides a springboard to dissect further how Piezos are regulated by mechanical force. Structure of the mechanically activated ion channel Piezo1.,Saotome K, Murthy SE, Kefauver JM, Whitwam T, Patapoutian A, Ward AB Nature. 2017 Dec 20. pii: nature25453. doi: 10.1038/nature25453. PMID:29261642[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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