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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-00636-4 |
| _version_ | 1818843832471519232 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T05:04:08Z |
| format | Article |
| id | doaj.art-a83fd16c95bb4f3381aa92bb9e0c15db |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T05:04:08Z |
| publishDate | 2017-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a83fd16c95bb4f3381aa92bb9e0c15db2022-12-21T20:34:59ZengNature PortfolioScientific Reports2045-23222017-04-017111010.1038/s41598-017-00636-4TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicityJason O. Sosa-Pagán0Edwin S. Iversen1Jörg Grandl2Department of Neurobiology, Duke University Medical CenterDepartment of Statistical Science, Duke UniversityDepartment of Neurobiology, Duke University Medical CenterAbstract 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.https://doi.org/10.1038/s41598-017-00636-4 |
| spellingShingle | Jason O. Sosa-Pagán Edwin S. Iversen Jörg Grandl TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-00636-4 |
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