Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Poster Abstracts

29-POS Board 8 CHARACTERIZING THE LIPID FINGERPRINT OF THE MECHANOSENSITIVE ION CHANNEL PIEZO2 Yie Chang Lin 1 ; Amanda Buyan 1 ; Ben Corry 1 ; 1 Australian National University, Research School of Biology, Canberra, Australia Piezo2 is a membrane-embedded mechanosensitive ion channel which mediates gentle touch sensations, tactile pain and proprioception. Ubiquitous depletion of Piezo2 in mice leads to early postnatal death, likely due to respiratory insufficiency. Additionally, malfunction of Piezo2 is known to cause mechanically induced pain syndromes and respiratory issues. Activated by mechanical stimuli such as membrane stretch and fluid flow, Piezo2 opens to allow cations to enter the cell. The cryo-EM structures of Piezo2 and its homologue Piezo1 shows that they consist of three subunits, forming a triskelion shape with curved propellers extending out from a central pore towards the extracellular space. In detergent and when reconstituted into liposomes, Piezo1 adopts a bowl-shaped conformation which induces local curvature within the bilayer, a feature thought to be critical for force sensing. As membrane proteins, Piezo channels affect and are affected by the surrounding lipid bilayer. In particular, Piezo channel function is known to be regulated by phosphoinositide lipids, cholesterol and dietary fatty acids. Recently, several studies have used molecular dynamics simulations to explore the interactions between Piezo1 and its lipid environment, revealing functionally important PIP2 and cholesterol binding sites on the protein. Given the recent elucidation of the Piezo2 cryo-EM structure and its similarities to Piezo1, molecular dynamics simulations of Piezo2 could yield interesting insights into its relationship with the bilayer and show whether it also induces local membrane curvature. Here, we present the characteristic lipid fingerprint of PIezo2 in a complex mammalian membrane, revealing key lipid-protein binding sites and highlighting its similarities and differences to the published Piezo1 lipid fingerprint.

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