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Progress in the Structural Basis of thermoTRP Channel Polymodal Gating
The thermosensory transient receptor potential (thermoTRP) family of ion channels is constituted by several nonselective cation channels that are activated by physical and chemical stimuli functioning as paradigmatic polymodal receptors. Gating of these ion channels is achieved through changes in te...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821180/ https://www.ncbi.nlm.nih.gov/pubmed/36614186 http://dx.doi.org/10.3390/ijms24010743 |
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author | Fernández-Ballester, Gregorio Fernández-Carvajal, Asia Ferrer-Montiel, Antonio |
author_facet | Fernández-Ballester, Gregorio Fernández-Carvajal, Asia Ferrer-Montiel, Antonio |
author_sort | Fernández-Ballester, Gregorio |
collection | PubMed |
description | The thermosensory transient receptor potential (thermoTRP) family of ion channels is constituted by several nonselective cation channels that are activated by physical and chemical stimuli functioning as paradigmatic polymodal receptors. Gating of these ion channels is achieved through changes in temperature, osmolarity, voltage, pH, pressure, and by natural or synthetic chemical compounds that directly bind to these proteins to regulate their activity. Given that thermoTRP channels integrate diverse physical and chemical stimuli, a thorough understanding of the molecular mechanisms underlying polymodal gating has been pursued, including the interplay between stimuli and differences between family members. Despite its complexity, recent advances in cryo-electron microscopy techniques are facilitating this endeavor by providing high-resolution structures of these channels in different conformational states induced by ligand binding or temperature that, along with structure-function and molecular dynamics, are starting to shed light on the underlying allosteric gating mechanisms. Because dysfunctional thermoTRP channels play a pivotal role in human diseases such as chronic pain, unveiling the intricacies of allosteric channel gating should facilitate the development of novel drug-based resolving therapies for these disorders. |
format | Online Article Text |
id | pubmed-9821180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98211802023-01-07 Progress in the Structural Basis of thermoTRP Channel Polymodal Gating Fernández-Ballester, Gregorio Fernández-Carvajal, Asia Ferrer-Montiel, Antonio Int J Mol Sci Review The thermosensory transient receptor potential (thermoTRP) family of ion channels is constituted by several nonselective cation channels that are activated by physical and chemical stimuli functioning as paradigmatic polymodal receptors. Gating of these ion channels is achieved through changes in temperature, osmolarity, voltage, pH, pressure, and by natural or synthetic chemical compounds that directly bind to these proteins to regulate their activity. Given that thermoTRP channels integrate diverse physical and chemical stimuli, a thorough understanding of the molecular mechanisms underlying polymodal gating has been pursued, including the interplay between stimuli and differences between family members. Despite its complexity, recent advances in cryo-electron microscopy techniques are facilitating this endeavor by providing high-resolution structures of these channels in different conformational states induced by ligand binding or temperature that, along with structure-function and molecular dynamics, are starting to shed light on the underlying allosteric gating mechanisms. Because dysfunctional thermoTRP channels play a pivotal role in human diseases such as chronic pain, unveiling the intricacies of allosteric channel gating should facilitate the development of novel drug-based resolving therapies for these disorders. MDPI 2023-01-01 /pmc/articles/PMC9821180/ /pubmed/36614186 http://dx.doi.org/10.3390/ijms24010743 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Fernández-Ballester, Gregorio Fernández-Carvajal, Asia Ferrer-Montiel, Antonio Progress in the Structural Basis of thermoTRP Channel Polymodal Gating |
title | Progress in the Structural Basis of thermoTRP Channel Polymodal Gating |
title_full | Progress in the Structural Basis of thermoTRP Channel Polymodal Gating |
title_fullStr | Progress in the Structural Basis of thermoTRP Channel Polymodal Gating |
title_full_unstemmed | Progress in the Structural Basis of thermoTRP Channel Polymodal Gating |
title_short | Progress in the Structural Basis of thermoTRP Channel Polymodal Gating |
title_sort | progress in the structural basis of thermotrp channel polymodal gating |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821180/ https://www.ncbi.nlm.nih.gov/pubmed/36614186 http://dx.doi.org/10.3390/ijms24010743 |
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