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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...

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Autores principales: Fernández-Ballester, Gregorio, Fernández-Carvajal, Asia, Ferrer-Montiel, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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