Figure 6
From: The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4 Signaling Pathway
MyD88- and TRIF- dependent downstream TLR pathways are mutually exclusive.
(a) TRAM-homodimer has a steric clash with Mal-homodimer when superimposed to BB TLR4-homodimer model and thus they are mutually exclusive: either Mal or TRAM homodimers can bind to TLR4 at any time. TRAM and Mal interactions are mutually exclusive in BB TLR4-homodimers and this is in line with the findings of several studies18,21,22. This indicates that MyD88-dependent pro-inflammatory and TRIF-dependent anti-inflammatory pathways are competitive. (b) TRAM-homodimer does not overlap with Mal-homodimer when superimposed to FF TLR4-homodimer model. (c) MyD88 overlaps with TRIF on TLR4: the FF TLR4-homodimer model has steric clashes of MyD88 and TRIF when superimposed Mal-MyD88 and TRAM-TRIF. Red box indicates the location of steric clash.
