This image shows a comparison of a TLR4 TIR domain model with the crystal structure of the TLR2 domain (left) or a TLR3 TIR model (right). It is obvious that some loop regions look very different in TLR3 vs 4 but not TLR2 vs 4, including the functionally important BB loop implicated in TIR-TIR interactions. This structural difference may explain the difference in adaptor protein specificity observed for different TLRs: Whereas TLR2 and 4 both bind MyD88 via Mal, TLR3 directly binds TRIF whereas TLR4 does not. Read more.