Biophysical Society Thematic Meeting | Trieste 2024

Emerging Theoretical Approaches to Complement Single-Particle Cryo-EM

Poster Abstracts

27-POS Board 27 A NONSPECIFIC CATION MEMBRANE CHANNEL PIEZO1 EMBEDDED IN A LIPID VESICLE Saša Svetina 1,2 ; Bojan Božic 2 ; 1 Jozef Stefan Institute, Department of Theoretical Physics, Ljubljana, Slovenia 2 Faculty of Medicine, University of Ljubljana, Institute of Biophysics, Ljubljana, Slovenia Piezo1 is a mechanosensitive protein known to respond to mechanical forces acting on cellular membranes. Several cryo-EM studies of solubilized Piezo1 revealed that it is a homotrimer whose three subunits construct its propeller-like shape by forming three spatially separated blades and a common central part containing the channel hole. A promising approach to study the mechanism of Piezo1 action are more recent cryo-EM studies of Piezo1 molecule embedded in a phospholipid vesicle [1-4]. They show that Piezo1 affects the shape of the vesicle membrane and also that the curvature of the surrounding membrane affects its own shape. The interpretation of these experiments requires the application of the theory of vesicle shape [3]. Here we describe the basics of this theory and report on the improvement of previous analyses [3-4] that makes it possible to identify from the measured vesicle shapes distinct Piezo1 conformations. [1] Y-C. Lin et al., Nature, 573, 230 (2019). [2] X. Yang et al., Nature, 604, 377 (2022). [3] C. A. Haselwandter et al., Proc. Nat. Acad. Sci, 119, e2208027119 (2022). [4] C. A. Haselwandter et al., Proc. Nat. Acad. Sci, 119, e2208034119 (2022 ).

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