MyD88 oligomerization within the complex of activated TLR 7/8 or 9 : MyD88

Structural analysis of MyD88:IRAK4 and MyD88:IRAK4:IRAK2 suggested that upon MyD88 recruitment to an activated dimerized TLR the MyD88 death domains clustering induces the formation of Mydosome, a large oligomeric signaling platform (Motshwene PG et al 2009, Lin SC et al 2010). Assembly of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. The oligomer complex stoichiometry was reported as 7:4 and 8:4 for MyD88:IRAK4 (Motshwene PG et al 2009), and 6:4:4 in the complex of MyD88:IRAK4:IRAK2(Lin SC et al 2010).

对MyD88:IRAK4及MyD88:IRAK4:IRAK2的结构分析表明，在MyD88被招募至激活的Toll样受体二聚体后，MyD88的死亡结构域的聚集引发Mydosome（一种大型寡聚信号平台）的形成（Motshwene PG 等人，2009年；Lin SC 等人，2010年）。这些Myddosome复合物的组装使得IRAKs的激酶结构域得以靠近，从而实现磷酸化和激活。据报道，MyD88:IRAK4的寡聚复合物化学计量比为7:4和8:4（Motshwene PG 等人，2009年），而MyD88:IRAK4:IRAK2复合物的化学计量比为6:4:4（Lin SC 等人，2010年）。