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Elevator-like movements of prestin mediate outer hair cell electromotility

The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SL...

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Autores principales: Kuwabara, Makoto F., Haddad, Bassam G., Lenz-Schwab, Dominik, Hartmann, Julia, Longo, Piersilvio, Huckschlag, Britt-Marie, Fuß, Anneke, Questino, Annalisa, Berger, Thomas K., Machtens, Jan-Philipp, Oliver, Dominik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628124/
https://www.ncbi.nlm.nih.gov/pubmed/37932294
http://dx.doi.org/10.1038/s41467-023-42489-8
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author Kuwabara, Makoto F.
Haddad, Bassam G.
Lenz-Schwab, Dominik
Hartmann, Julia
Longo, Piersilvio
Huckschlag, Britt-Marie
Fuß, Anneke
Questino, Annalisa
Berger, Thomas K.
Machtens, Jan-Philipp
Oliver, Dominik
author_facet Kuwabara, Makoto F.
Haddad, Bassam G.
Lenz-Schwab, Dominik
Hartmann, Julia
Longo, Piersilvio
Huckschlag, Britt-Marie
Fuß, Anneke
Questino, Annalisa
Berger, Thomas K.
Machtens, Jan-Philipp
Oliver, Dominik
author_sort Kuwabara, Makoto F.
collection PubMed
description The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SLC26A5). We used a combination of molecular dynamics (MD) simulations and biophysical approaches to identify the structural dynamics of prestin that mediate eM. MD simulations showed that prestin samples a vast conformational landscape with expanded (ES) and compact (CS) states beyond previously reported prestin structures. Transition from CS to ES is dominated by the translational-rotational movement of prestin’s transport domain, akin to elevator-type substrate translocation by related solute carriers. Reversible transition between CS and ES states was supported experimentally by cysteine accessibility scanning, cysteine cross-linking between transport and scaffold domains, and voltage-clamp fluorometry (VCF). Our data demonstrate that prestin’s piezoelectric dynamics recapitulate essential steps of a structurally conserved ion transport cycle.
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spelling pubmed-106281242023-11-08 Elevator-like movements of prestin mediate outer hair cell electromotility Kuwabara, Makoto F. Haddad, Bassam G. Lenz-Schwab, Dominik Hartmann, Julia Longo, Piersilvio Huckschlag, Britt-Marie Fuß, Anneke Questino, Annalisa Berger, Thomas K. Machtens, Jan-Philipp Oliver, Dominik Nat Commun Article The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SLC26A5). We used a combination of molecular dynamics (MD) simulations and biophysical approaches to identify the structural dynamics of prestin that mediate eM. MD simulations showed that prestin samples a vast conformational landscape with expanded (ES) and compact (CS) states beyond previously reported prestin structures. Transition from CS to ES is dominated by the translational-rotational movement of prestin’s transport domain, akin to elevator-type substrate translocation by related solute carriers. Reversible transition between CS and ES states was supported experimentally by cysteine accessibility scanning, cysteine cross-linking between transport and scaffold domains, and voltage-clamp fluorometry (VCF). Our data demonstrate that prestin’s piezoelectric dynamics recapitulate essential steps of a structurally conserved ion transport cycle. Nature Publishing Group UK 2023-11-06 /pmc/articles/PMC10628124/ /pubmed/37932294 http://dx.doi.org/10.1038/s41467-023-42489-8 Text en © The Author(s) 2023 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
Kuwabara, Makoto F.
Haddad, Bassam G.
Lenz-Schwab, Dominik
Hartmann, Julia
Longo, Piersilvio
Huckschlag, Britt-Marie
Fuß, Anneke
Questino, Annalisa
Berger, Thomas K.
Machtens, Jan-Philipp
Oliver, Dominik
Elevator-like movements of prestin mediate outer hair cell electromotility
title Elevator-like movements of prestin mediate outer hair cell electromotility
title_full Elevator-like movements of prestin mediate outer hair cell electromotility
title_fullStr Elevator-like movements of prestin mediate outer hair cell electromotility
title_full_unstemmed Elevator-like movements of prestin mediate outer hair cell electromotility
title_short Elevator-like movements of prestin mediate outer hair cell electromotility
title_sort elevator-like movements of prestin mediate outer hair cell electromotility
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628124/
https://www.ncbi.nlm.nih.gov/pubmed/37932294
http://dx.doi.org/10.1038/s41467-023-42489-8
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