Death domain of Myeloid Differentation primary response protein MyD88
Death Domain (DD) of Myeloid Differentiation primary response protein 88 (MyD88). MyD88 is an adaptor protein involved in interleukin-1 receptor (IL-1R)- and Toll-like receptor (TLR)-induced activation of nuclear factor-kappaB (NF-kB) and mitogen activated protein kinase pathways that lead to the induction of proinflammatory cytokines. It is a key component in the signaling pathway of pathogen recognition in the innate immune system. MyD88 contains an N-terminal DD and a C-terminal Toll/IL-1 Receptor (TIR) homology domain that mediates interaction with TLRs and IL-1R. In general, 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:MyD88-IRAK4 interaction site [polypeptide binding site]
Evidence:
Structure:3MOP; Four MyD88 DDs interact with four IRAK4 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.",