TIR enzymatic functions: signaling molecules and receptor mechanisms

The evolutionarily conserved Toll/Interleukin-1 Receptor (TIR) domains across kingdoms of prokaryotes, plants, and animals play critical roles in innate immunity. Recent studies have revealed the enzymatic functions of TIRs, the structural bases of TIRs as holoenzymes, and the identity of TIR-generated small signaling molecules and their receptors, which significantly advanced our understanding on TIR-mediated immune signaling pathways. We reviewed the most up-to-date findings in TIR enzymatic functions from the perspectives of signaling molecules and receptor mechanisms.