Figure 8
From: The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4 Signaling Pathway
Parallel downstream pathways of TLRs, which lead to distinct outcomes, are mutually exclusive.
Green arrows shows that TRIF- and MyD88-dependent paths cannot be activated simultaneously due to shared binding sites on TLR4-dimer or steric hindrance. Blue arrows demonstrate that TRAF6 and TRAF3 bind to overlapping interfaces on MyD88 DD (downstream of endosomal TLRs). Pink arrows shows that IRAK4 and FADD will have steric clash when they bind to MyD88 at the same time. The three branches of TLR pathway, namely pro-inflammatory, interferon and anti-inflammatory and apoptotic paths are mutually exclusive.
