Figure 2
From: The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4 Signaling Pathway
3D schematic view of TIR-domain signalosome, myddosome and TLR clustering.
It is known that TLRs cluster on lipid rafts, but they cannot tetramerize due to the steric hindrance of their ectodomains26,34. Oligomerization of the downstream proteins may hold TLRs together. Here, all TIR domains are in dimer form, TLR4, Mal and MyD88. A TLR4-dimer recruits two Mal-dimers, which in turn recruit four MyD88-dimers. In the myddosome complexes, there are six MyD88 molecules, four IRAK4 and four IRAK2. The box at the upper right corner shows the cartoon version of the model. The PDB_ID of the myddosome complex is 3mop: MyD88 death domains 3mopBCDE, IRAK4 death domains 3mopGHIJ, IRAK2 death domains 3mopKLMN. Pink circles are PI(4,5)P2, which are enriched in lipid rafts and N-terminal region of Mal associates with it.
