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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sosa-Pagán, JO; Iversen, ES; Grandl, J

Published Date

  • April 3, 2017

Published In

Volume / Issue

  • 7 / 1

Start / End Page

  • 549 -

PubMed ID

  • 28373693

Pubmed Central ID

  • 28373693

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

International Standard Serial Number (ISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-017-00636-4

Language

  • eng