Francisco Enguita's profile

Mouse Piezo1 mechanosensor

Mechanosensitive Piezo channels form a small protein family encompassing only two paralogs in vertebrates, Piezo1 and Piezo2. In spite of their small family size, these channels undertake many important physiological functions in adult and developing animals, including osmotic homeostasis, visceral, and somatic mechanosensation, proprioception, blood flow sensing, and epithelial homeostasis. Abnormal Piezo channel activity caused by inherited mutations, genetic manipulation or physiological regulation has been linked to a variety of pathological conditions such as xerocytosis, lymphedema, arthrogryposis, abnormal vascular development, sleep apnea, allodynia and the loss of proprioception. Piezo1, the best studied Piezo channel, opens upon direct physical deformations of the lipid bilayer, such as increased membrane tension, and thus obeys the so-called force-from-lipid paradigm established for several mechanosensitive ion channels. Recent advances in cryo-electron microscopy (cryo-EM) have enabled the capture of mouse Piezo1 (mPZ1) in non-conducting states, which presumably correspond to the canonical closed conformation populated in absence of external mechanical force. These structures reveal a propeller-like structure with a central pore surrounded by three large peripheral domains called arms, or blades. Each of these peripheral domains is formed by a succession of helical bundles called Piezo repeats, or transmembrane helical units, and are connected to long intracellular beams that extend toward the intracellular side of the pore. You can see this folding exemplified by the cryoEM structure of the mouse Piezo1 protein (PDB code: 7WLT)

#molecularart ... #immolecular ... #piezo ... #mechanical ... #force ... #sensor ... #membrane ... #helix ... #channel ... #cryoem

Piezo1 channel structure was rendered by @proteinimaging and depicted using @corelphotopaint

Mouse Piezo1 mechanosensor
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Mouse Piezo1 mechanosensor

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