title: Toll/interleukin-1 receptor domain dimers as the platform for activation and enhanced inhibition of Toll-like receptor signaling.
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.
authors: Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana, Slovenia.
authors: Ota
authors: O
authors: Fekonja
authors: Mojca
authors: M
authors: Benčina
authors: Roman
authors: R
authors: Jerala
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors