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Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors
Ligand-gated ion channels enable intercellular transmission of action potential through synapses by transducing biochemical messengers into electrical signal. We designed artificial ligand-gated ion channels by coupling G protein-coupled receptors to the Kir6.2 potassium channel. These artificial ch...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286527/ https://www.ncbi.nlm.nih.gov/pubmed/28145461 http://dx.doi.org/10.1038/srep41154 |
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author | Moreau, Christophe J. Revilloud, Jean Caro, Lydia N. Dupuis, Julien P. Trouchet, Amandine Estrada-Mondragón, Argel Nieścierowicz, Katarzyna Sapay, Nicolas Crouzy, Serge Vivaudou, Michel |
author_facet | Moreau, Christophe J. Revilloud, Jean Caro, Lydia N. Dupuis, Julien P. Trouchet, Amandine Estrada-Mondragón, Argel Nieścierowicz, Katarzyna Sapay, Nicolas Crouzy, Serge Vivaudou, Michel |
author_sort | Moreau, Christophe J. |
collection | PubMed |
description | Ligand-gated ion channels enable intercellular transmission of action potential through synapses by transducing biochemical messengers into electrical signal. We designed artificial ligand-gated ion channels by coupling G protein-coupled receptors to the Kir6.2 potassium channel. These artificial channels called ion channel-coupled receptors offer complementary properties to natural channels by extending the repertoire of ligands to those recognized by the fused receptors, by generating more sustained signals and by conferring potassium selectivity. The first artificial channels based on the muscarinic M2 and the dopaminergic D2(L) receptors were opened and closed by acetylcholine and dopamine, respectively. We find here that this opposite regulation of the gating is linked to the length of the receptor C-termini, and that C-terminus engineering can precisely control the extent and direction of ligand gating. These findings establish the design rules to produce customized ligand-gated channels for synthetic biology applications. |
format | Online Article Text |
id | pubmed-5286527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52865272017-02-06 Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors Moreau, Christophe J. Revilloud, Jean Caro, Lydia N. Dupuis, Julien P. Trouchet, Amandine Estrada-Mondragón, Argel Nieścierowicz, Katarzyna Sapay, Nicolas Crouzy, Serge Vivaudou, Michel Sci Rep Article Ligand-gated ion channels enable intercellular transmission of action potential through synapses by transducing biochemical messengers into electrical signal. We designed artificial ligand-gated ion channels by coupling G protein-coupled receptors to the Kir6.2 potassium channel. These artificial channels called ion channel-coupled receptors offer complementary properties to natural channels by extending the repertoire of ligands to those recognized by the fused receptors, by generating more sustained signals and by conferring potassium selectivity. The first artificial channels based on the muscarinic M2 and the dopaminergic D2(L) receptors were opened and closed by acetylcholine and dopamine, respectively. We find here that this opposite regulation of the gating is linked to the length of the receptor C-termini, and that C-terminus engineering can precisely control the extent and direction of ligand gating. These findings establish the design rules to produce customized ligand-gated channels for synthetic biology applications. Nature Publishing Group 2017-02-01 /pmc/articles/PMC5286527/ /pubmed/28145461 http://dx.doi.org/10.1038/srep41154 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Moreau, Christophe J. Revilloud, Jean Caro, Lydia N. Dupuis, Julien P. Trouchet, Amandine Estrada-Mondragón, Argel Nieścierowicz, Katarzyna Sapay, Nicolas Crouzy, Serge Vivaudou, Michel Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors |
title | Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors |
title_full | Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors |
title_fullStr | Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors |
title_full_unstemmed | Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors |
title_short | Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors |
title_sort | tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of g protein-coupled receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286527/ https://www.ncbi.nlm.nih.gov/pubmed/28145461 http://dx.doi.org/10.1038/srep41154 |
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