Death domain of Interleukin-1 Receptor-Associated Kinase 4.
Death Domain (DD) of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4). IRAKs are essential components of innate immunity and inflammation in mammals and other vertebrates. They are involved in signal transduction pathways involving IL-1 and IL-18 receptors, Toll-like receptors, nuclear factor-kappaB, and mitogen-activated protein kinases. IRAKs contain an N-terminal DD domain and a C-terminal kinase domain. IRAK4 is an active kinase that is also involved in T-cell receptor signaling pathways, implying that it may function in acquired immunity and not just in innate immunity. It is known as the master IRAK member because its absence strongly impairs TLR- and IL-1-mediated signaling and innate immune defenses, while the absence of other IRAK proteins only shows slight effects. IRAK4-deficient patients have impaired inflammatory responses and recurrent life-threatening infections. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.
Feature 1:IRAK4-MyD88 interaction site [polypeptide binding site]
Evidence:
Structure:3MOP; Four IRAK4 DDs interact with four MyD88 DDs within the Myddosome complex; contacts at 4A.
Comment:MyD88, IRAK4, and IRAK2 form the Myddosome complex which is assembled in a stepwise manner. MyD88 first recruits IRAK4, then the MyD88-IRAK4 complex recruits the substrates IRAK2 or IRAK1.
Jiyao W et al.(2023). "The conserved domain database in 2023.",