Toll/interleukin-1 receptor domain dimers as the platform for activation and enhanced inhibition of Toll-like receptor signaling.
J Biol Chem
; 287(37): 30993-1002, 2012 Sep 07.
Article
em En
| MEDLINE
| ID: mdl-22829600
ABSTRACT
TIR (Toll/IL-1 receptor) domains mediate interactions between TLR (Toll-like) or IL-1 family receptors and signaling adapters. While homotypic TIR domain interactions mediate receptor activation they are also usurped by microbial TIR domain containing proteins for immunosuppression. Here we show the role of a dimerized TIR domain platform for the suppression as well as for the activation of MyD88 signaling pathway. Coiled-coil dimerization domain, present in many bacterial TCPs, potently augments suppression of TLR/IL-1R signaling. The addition of a strong coiled-coil dimerization domain conferred the superior inhibition against the wide spectrum of TLRs and prevented the constitutive activation by a dimeric TIR platform. We propose a molecular model of MyD88-mediated signaling based on the dimerization of TIR domains as the limiting step.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Receptores de Interleucina-1
/
Receptores Toll-Like
/
Multimerização Proteica
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article