TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity

Abstract Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jason O. Sosa-Pagán, Edwin S. Iversen, Jörg Grandl
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a83fd16c95bb4f3381aa92bb9e0c15db
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a83fd16c95bb4f3381aa92bb9e0c15db
record_format	dspace
spelling	oai:doaj.org-article:a83fd16c95bb4f3381aa92bb9e0c15db2021-12-02T11:52:32ZTRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity10.1038/s41598-017-00636-42045-2322https://doaj.org/article/a83fd16c95bb4f3381aa92bb9e0c15db2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00636-4https://doaj.org/toc/2045-2322Abstract Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes that temperature activation is driven by the exposure of hydrophobic residues to solvent. This mechanism further predicts that residues are exposed to solvent in a coordinated fashion, but without necessarily being located in close proximity to each other. However, there is little experimental evidence supporting this mechanism in TRP channels. Here, we combined high-throughput mutagenesis, functional screening, and deep sequencing to identify mutations from a total of ~7,300 TRPV1 random mutant clones. We found that strong decreases in hydrophobicity of amino acids are better tolerated for activation by capsaicin than for activation by hot temperature, suggesting that strong hydrophobicity might be specifically required for temperature activation. Altogether, our work provides initial correlative support for a previously hypothesized temperature mechanism in TRP ion channels.Jason O. Sosa-PagánEdwin S. IversenJörg GrandlNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jason O. Sosa-Pagán Edwin S. Iversen Jörg Grandl TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity
description	Abstract Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes that temperature activation is driven by the exposure of hydrophobic residues to solvent. This mechanism further predicts that residues are exposed to solvent in a coordinated fashion, but without necessarily being located in close proximity to each other. However, there is little experimental evidence supporting this mechanism in TRP channels. Here, we combined high-throughput mutagenesis, functional screening, and deep sequencing to identify mutations from a total of ~7,300 TRPV1 random mutant clones. We found that strong decreases in hydrophobicity of amino acids are better tolerated for activation by capsaicin than for activation by hot temperature, suggesting that strong hydrophobicity might be specifically required for temperature activation. Altogether, our work provides initial correlative support for a previously hypothesized temperature mechanism in TRP ion channels.
format	article
author	Jason O. Sosa-Pagán Edwin S. Iversen Jörg Grandl
author_facet	Jason O. Sosa-Pagán Edwin S. Iversen Jörg Grandl
author_sort	Jason O. Sosa-Pagán
title	TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity
title_short	TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity
title_full	TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity
title_fullStr	TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity
title_full_unstemmed	TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity
title_sort	trpv1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a83fd16c95bb4f3381aa92bb9e0c15db
work_keys_str_mv	AT jasonososapagan trpv1temperatureactivationisspecificallysensitivetostrongdecreasesinaminoacidhydrophobicity AT edwinsiversen trpv1temperatureactivationisspecificallysensitivetostrongdecreasesinaminoacidhydrophobicity AT jorggrandl trpv1temperatureactivationisspecificallysensitivetostrongdecreasesinaminoacidhydrophobicity
_version_	1718395003526447104

TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity

Ejemplares similares