Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Moreau, Christophe J., Revilloud, Jean, Caro, Lydia N., Dupuis, Julien P., Trouchet, Amandine, Estrada-Mondragón, Argel, Nieścierowicz, Katarzyna, Sapay, Nicolas, Crouzy, Serge, Vivaudou, Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
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
_version_ 1782504019168591872
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
work_keys_str_mv AT moreauchristophej tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT revilloudjean tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT carolydian tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT dupuisjulienp tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT trouchetamandine tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT estradamondragonargel tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT niescierowiczkatarzyna tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT sapaynicolas tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT crouzyserge tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors
AT vivaudoumichel tuningtheallostericregulationofartificialmuscarinicanddopaminergicligandgatedpotassiumchannelsbyproteinengineeringofgproteincoupledreceptors