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Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification

Prestin is a high-density motor protein in the outer hair cells (OHCs), whose conformational response to acoustic signals alters the shape of the cell, thereby playing a major role in sound amplification by the cochlea. Despite recent structures, prestin’s intimate interactions with the membrane, wh...

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Autores principales: Dehghani-Ghahnaviyeh, Sepehr, Zhao, Zhiyu, Tajkhorshid, Emad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653410/
https://www.ncbi.nlm.nih.gov/pubmed/36371434
http://dx.doi.org/10.1038/s41467-022-34596-9
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author Dehghani-Ghahnaviyeh, Sepehr
Zhao, Zhiyu
Tajkhorshid, Emad
author_facet Dehghani-Ghahnaviyeh, Sepehr
Zhao, Zhiyu
Tajkhorshid, Emad
author_sort Dehghani-Ghahnaviyeh, Sepehr
collection PubMed
description Prestin is a high-density motor protein in the outer hair cells (OHCs), whose conformational response to acoustic signals alters the shape of the cell, thereby playing a major role in sound amplification by the cochlea. Despite recent structures, prestin’s intimate interactions with the membrane, which are central to its function remained unresolved. Here, employing a large set (collectively, more than 0.5 ms) of coarse-grained molecular dynamics simulations, we demonstrate the impact of prestin’s lipid-protein interactions on its organization at densities relevant to the OHCs and its effectiveness in reshaping OHCs. Prestin causes anisotropic membrane deformation, which mediates a preferential membrane organization of prestin where deformation patterns by neighboring copies are aligned constructively. The resulting reduced membrane rigidity is hypothesized to maximize the impact of prestin on OHC reshaping. These results demonstrate a clear case of protein-protein cooperative communication in membrane, purely mediated by interactions with lipids.
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spelling pubmed-96534102022-11-15 Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification Dehghani-Ghahnaviyeh, Sepehr Zhao, Zhiyu Tajkhorshid, Emad Nat Commun Article Prestin is a high-density motor protein in the outer hair cells (OHCs), whose conformational response to acoustic signals alters the shape of the cell, thereby playing a major role in sound amplification by the cochlea. Despite recent structures, prestin’s intimate interactions with the membrane, which are central to its function remained unresolved. Here, employing a large set (collectively, more than 0.5 ms) of coarse-grained molecular dynamics simulations, we demonstrate the impact of prestin’s lipid-protein interactions on its organization at densities relevant to the OHCs and its effectiveness in reshaping OHCs. Prestin causes anisotropic membrane deformation, which mediates a preferential membrane organization of prestin where deformation patterns by neighboring copies are aligned constructively. The resulting reduced membrane rigidity is hypothesized to maximize the impact of prestin on OHC reshaping. These results demonstrate a clear case of protein-protein cooperative communication in membrane, purely mediated by interactions with lipids. Nature Publishing Group UK 2022-11-12 /pmc/articles/PMC9653410/ /pubmed/36371434 http://dx.doi.org/10.1038/s41467-022-34596-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Dehghani-Ghahnaviyeh, Sepehr
Zhao, Zhiyu
Tajkhorshid, Emad
Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification
title Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification
title_full Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification
title_fullStr Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification
title_full_unstemmed Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification
title_short Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification
title_sort lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653410/
https://www.ncbi.nlm.nih.gov/pubmed/36371434
http://dx.doi.org/10.1038/s41467-022-34596-9
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