The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4 Signaling Pathway.

ABSTRACT: Activated Toll-like receptors (TLRs) cluster in lipid rafts and induce pro- and anti-tumor responses. The organization of the assembly is critical to the understanding of how these key receptors control major signaling pathways in the cell. Although several models for individual interactions were proposed, the entire TIR-domain signalosome architecture has not been worked out, possibly due to its complexity. We employ a powerful algorithm, crystal structures and experimental data to model the TLR4 and its cluster. The architecture that we obtain with 8 MyD88 molecules provides the structural basis for the MyD88-templated myddosome helical assembly and receptor clustering; it also provides clues to pro- and anti-inflammatory signaling pathways branching at the signalosome level to Mal/MyD88

SUBMITTER: Guven-Maiorov E 

PROVIDER: S-EPMC4544004 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature