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Principles of agonist recognition in Cys-loop receptors

Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine, and GABA. After the term “chemoreceptor” emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning,...

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Autores principales: Lynagh, Timothy, Pless, Stephan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006026/
https://www.ncbi.nlm.nih.gov/pubmed/24795655
http://dx.doi.org/10.3389/fphys.2014.00160
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author Lynagh, Timothy
Pless, Stephan A.
author_facet Lynagh, Timothy
Pless, Stephan A.
author_sort Lynagh, Timothy
collection PubMed
description Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine, and GABA. After the term “chemoreceptor” emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies, and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands.
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spelling pubmed-40060262014-05-02 Principles of agonist recognition in Cys-loop receptors Lynagh, Timothy Pless, Stephan A. Front Physiol Physiology Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine, and GABA. After the term “chemoreceptor” emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies, and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands. Frontiers Media S.A. 2014-04-24 /pmc/articles/PMC4006026/ /pubmed/24795655 http://dx.doi.org/10.3389/fphys.2014.00160 Text en Copyright © 2014 Lynagh and Pless. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Lynagh, Timothy
Pless, Stephan A.
Principles of agonist recognition in Cys-loop receptors
title Principles of agonist recognition in Cys-loop receptors
title_full Principles of agonist recognition in Cys-loop receptors
title_fullStr Principles of agonist recognition in Cys-loop receptors
title_full_unstemmed Principles of agonist recognition in Cys-loop receptors
title_short Principles of agonist recognition in Cys-loop receptors
title_sort principles of agonist recognition in cys-loop receptors
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006026/
https://www.ncbi.nlm.nih.gov/pubmed/24795655
http://dx.doi.org/10.3389/fphys.2014.00160
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