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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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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. |
format | Online Article Text |
id | pubmed-6168238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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