Chong, J orcid.org/0000-0002-5846-7397, De Vecchis, D, Hyman, AJ et al. (5 more authors) (2021) Modelling of full-length Piezo1 suggests importance of the proximal N-terminus for dome structure. Biophysical Journal, 120 (8). pp. 1343-1356. ISSN 0006-3495
Abstract
Piezo1 forms a mechanically activated calcium-permeable nonselective cation channel that is functionally important in many cell types. Structural data exist for C-terminal regions, but we lack information about N-terminal regions and how the entire channel interacts with the lipid bilayer. Here, we use computational approaches to predict the three-dimensional structure of the full-length Piezo1 and simulate it in an asymmetric membrane. A number of novel insights are suggested by the model: 1) Piezo1 creates a trilobed dome in the membrane that extends beyond the radius of the protein, 2) Piezo1 changes the lipid environment in its vicinity via preferential interactions with cholesterol and phosphatidylinositol 4,5-bisphosphate (PIP2) molecules, and 3) cholesterol changes the depth of the dome and PIP2 binding preference. In vitro alteration of cholesterol concentration inhibits Piezo1 activity in a manner complementing some of our computational findings. The data suggest the importance of N-terminal regions of Piezo1 for dome structure and membrane cholesterol and PIP2 interactions.
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Copyright, Publisher and Additional Information: | © 2021 Biophysical Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | ||||||||
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Institution: | The University of Leeds | ||||||||
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) | ||||||||
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Depositing User: | Symplectic Publications | ||||||||
Date Deposited: | 05 Feb 2021 16:51 | ||||||||
Last Modified: | 25 Jun 2023 22:34 | ||||||||
Status: | Published | ||||||||
Publisher: | Biophysical Society | ||||||||
Identification Number: | https://doi.org/10.1016/j.bpj.2021.02.003 |