Current View of Ligand and Lipid Recognition by the Menthol Receptor TRPM8.
Trends Biochem Sci
; 45(9): 806-819, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32532587
ABSTRACT
Transient receptor potential (TRP) melastatin member 8 (TRPM8), which is a calcium-permeable ion channel, functions as the primary molecular sensor of cold and menthol in humans. Recent cryoelectron microscopy (cryo-EM) studies of TRPM8 have shown distinct structural features in its architecture and domain assembly compared with the capsaicin receptor TRP vanilloid member 1 (TRPV1). Moreover, ligand-bound TRPM8 structures have uncovered unforeseen binding sites for both cooling agonists and membrane lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. These complex structures unveil the molecular basis of cooling agonist sensing by TRPM8 and the allosteric role of PI(4,5)P2 in agonist binding for TRPM8 activation. Here, we review the recent advances in TRPM8 structural biology and investigate the molecular principles governing the distinguishing role of TRPM8 as the evolutionarily conserved menthol receptor.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Canales Catiónicos TRPM
/
Mentol
Límite:
Humans
Idioma:
En
Revista:
Trends Biochem Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos