The capsaicin binding affinity of wildtype and mutant TRPV1 ion channels.
J Biol Chem
; 299(11): 105268, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37734552
ABSTRACT
Vanilloids such as capsaicin and resiniferatoxin are highly selective and potent activators for transient receptor potential vanilloid subfamily, member 1, a nociceptor for heat and pain perception. However, the intrinsic vanilloid binding affinity, key for understanding transient receptor potential vanilloid subfamily, member 1 function, remains unknown despite intensive investigations by electrophysiological, structural, and computational methods. In this study, we determined capsaicin binding affinity under physiological conditions by isolating individual binding steps to each subunit with concatemers. We estimated the capsaicin association constant of a wildtype subunit to be in the order of 106 M-1 and that of the Y511A mutant subunit to be a hundred times lower, in the order of 104 M-1. The Y511A mutation, located at the entrance of the vanilloid binding pocket, reduces binding affinity without a noticeable effect on activation gating. We further affirmed that there is little cooperativity between vanilloid binding steps. Models based on independent binding and equally cooperative subunit gating can accurately describe capsaicin activation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Capsaicina
/
Canais de Cátion TRPV
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos