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Determining the molecular basis of voltage sensitivity in membrane proteins

Voltage-sensitive membrane proteins are united by their ability to transform changes in membrane potential into mechanical work. They are responsible for a spectrum of physiological processes in living organisms, including electrical signaling and cell-cycle progression. Although the mechanism of vo...

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Autores principales: Kasimova, Marina A., Lindahl, Erik, Delemotte, Lucie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168238/
https://www.ncbi.nlm.nih.gov/pubmed/30150239
http://dx.doi.org/10.1085/jgp.201812086
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author Kasimova, Marina A.
Lindahl, Erik
Delemotte, Lucie
author_facet Kasimova, Marina A.
Lindahl, Erik
Delemotte, Lucie
author_sort Kasimova, Marina A.
collection PubMed
description Voltage-sensitive membrane proteins are united by their ability to transform changes in membrane potential into mechanical work. They are responsible for a spectrum of physiological processes in living organisms, including electrical signaling and cell-cycle progression. Although the mechanism of voltage-sensing has been well characterized for some membrane proteins, including voltage-gated ion channels, even the location of the voltage-sensing elements remains unknown for others. Moreover, the detection of these elements by using experimental techniques is challenging because of the diversity of membrane proteins. Here, we provide a computational approach to predict voltage-sensing elements in any membrane protein, independent of its structure or function. It relies on an estimation of the propensity of a protein to respond to changes in membrane potential. We first show that this property correlates well with voltage sensitivity by applying our approach to a set of voltage-sensitive and voltage-insensitive membrane proteins. We further show that it correctly identifies authentic voltage-sensitive residues in the voltage-sensor domain of voltage-gated ion channels. Finally, we investigate six membrane proteins for which the voltage-sensing elements have not yet been characterized and identify residues and ions that might be involved in the response to voltage. The suggested approach is fast and simple and enables a characterization of voltage sensitivity that goes beyond mere identification of charges. We anticipate that its application before mutagenesis experiments will significantly reduce the number of potential voltage-sensitive elements to be tested.
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spelling pubmed-61682382019-04-01 Determining the molecular basis of voltage sensitivity in membrane proteins Kasimova, Marina A. Lindahl, Erik Delemotte, Lucie J Gen Physiol Research Articles Voltage-sensitive membrane proteins are united by their ability to transform changes in membrane potential into mechanical work. They are responsible for a spectrum of physiological processes in living organisms, including electrical signaling and cell-cycle progression. Although the mechanism of voltage-sensing has been well characterized for some membrane proteins, including voltage-gated ion channels, even the location of the voltage-sensing elements remains unknown for others. Moreover, the detection of these elements by using experimental techniques is challenging because of the diversity of membrane proteins. Here, we provide a computational approach to predict voltage-sensing elements in any membrane protein, independent of its structure or function. It relies on an estimation of the propensity of a protein to respond to changes in membrane potential. We first show that this property correlates well with voltage sensitivity by applying our approach to a set of voltage-sensitive and voltage-insensitive membrane proteins. We further show that it correctly identifies authentic voltage-sensitive residues in the voltage-sensor domain of voltage-gated ion channels. Finally, we investigate six membrane proteins for which the voltage-sensing elements have not yet been characterized and identify residues and ions that might be involved in the response to voltage. The suggested approach is fast and simple and enables a characterization of voltage sensitivity that goes beyond mere identification of charges. We anticipate that its application before mutagenesis experiments will significantly reduce the number of potential voltage-sensitive elements to be tested. Rockefeller University Press 2018-10-01 /pmc/articles/PMC6168238/ /pubmed/30150239 http://dx.doi.org/10.1085/jgp.201812086 Text en © 2018 Kasimova et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Kasimova, Marina A.
Lindahl, Erik
Delemotte, Lucie
Determining the molecular basis of voltage sensitivity in membrane proteins
title Determining the molecular basis of voltage sensitivity in membrane proteins
title_full Determining the molecular basis of voltage sensitivity in membrane proteins
title_fullStr Determining the molecular basis of voltage sensitivity in membrane proteins
title_full_unstemmed Determining the molecular basis of voltage sensitivity in membrane proteins
title_short Determining the molecular basis of voltage sensitivity in membrane proteins
title_sort determining the molecular basis of voltage sensitivity in membrane proteins
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168238/
https://www.ncbi.nlm.nih.gov/pubmed/30150239
http://dx.doi.org/10.1085/jgp.201812086
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