TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity.
Sci Rep
; 7(1): 549, 2017 04 03.
Article
en En
| MEDLINE
| ID: mdl-28373693
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Temperatura
/
Activación del Canal Iónico
/
Canales Catiónicos TRPV
/
Interacciones Hidrofóbicas e Hidrofílicas
/
Aminoácidos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido