Structure and regulation of cytoplasmic adapter proteins involved in innate immune signaling

Initiation of the innate immune response requires agonist recognition by a pathogen recognition receptor. Following ligand binding, conformational rearrangement of the receptor creates a molecular scaffold from which signal transduction is propagated via complex cellular signaling pathways. This in turn leads to the induction of a pro-inflammatory immune response. A critical component of these signaling pathways is the homotypic interaction of receptor and adapter proteins via specific protein interaction domains. Within the innate immune signaling cascade, homotypic interactions between members of the death domain family and the Toll/interleukin-1 receptor domain are particularly important. Here we discuss the current understanding of the molecular basis of these homotypic receptor:adapter interactions and their role in innate immune signal transduction.