Targeting TLR/IL-1R Signalling in Human Diseases

Figure 3

Schematic representation of the TIR and Death Domains of MyD88. (a) A schematic representation of the human MyD88 TIR domain. The TIR domain of MyD88 consists of five central $\beta$-strands surrounded by four $\alpha$-helices, connected by loops [36]. It lacks the $\alpha$-helix $\alpha$D in the region between $\beta$D and $\beta$E strands, this region has an helical coil conformation. (b) Surface of interaction of the MyD88 Death Domain with IRAK1 and IRAK4. The region MyD88 Death Domain (DD) comprised by residues 27–72 (predicted $\alpha$1, $\alpha$2, $\alpha$3 and N-terminal $\alpha$4 helices) is required for the recruitment of IRAK1 [37]. Residues E52 and Y58 of MyD88 DD are implicated in the interaction of IRAK1 with MyD88. Moreover, residue K95 in the predicted $\alpha$5 helix is involved in the recruitment of IRAK4 by MyD88 DD.

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