The structural basis for an on-off switch controlling Gßγ-mediated inhibition of TRPM3 channels.
Proc Natl Acad Sci U S A
; 117(46): 29090-29100, 2020 11 17.
Article
en En
| MEDLINE
| ID: mdl-33122432
ABSTRACT
TRPM3 channels play important roles in the detection of noxious heat and in inflammatory thermal hyperalgesia. The activity of these ion channels in somatosensory neurons is tightly regulated by µ-opioid receptors through the signaling of Gßγ proteins, thereby reducing TRPM3-mediated pain. We show here that Gßγ directly binds to a domain of 10 amino acids in TRPM3 and solve a cocrystal structure of this domain together with Gßγ. Using these data and mutational analysis of full-length proteins, we pinpoint three amino acids in TRPM3 and their interacting partners in Gß1 that are individually necessary for TRPM3 inhibition by Gßγ. The 10-amino-acid Gßγ-interacting domain in TRPM3 is subject to alternative splicing. Its inclusion in or exclusion from TRPM3 channel proteins therefore provides a mechanism for switching on or off the inhibitory action that Gßγ proteins exert on TRPM3 channels.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Subunidades beta de la Proteína de Unión al GTP
/
Subunidades gamma de la Proteína de Unión al GTP
/
Canales Catiónicos TRPM
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania