An important category of innate immune plant NLRs carry a TIR (Toll/interleukin-1 receptor, resistance) signalling domain at their N-termini. The molecular mechanism of plant TIRs once activated is unknown. Much of what we have learnt about plant TIRs has come from our studies of animal TIR-containing proteins. Assemblies of TLR (Toll-like receptor) adaptor TIR domains can be produced in vitro and the structure of the MAL (MyD88 adaptor-like protein) filamentous assembly has been determined by cryo-EM. Plant TIR domains can also self-associate through more than one interface. The crystal structure of the TIR domain from the catalytically active protein SARM1 (sterile alpha and armadillo-motif containing protein), involved in a cell death pathway operating within neurons, has also been determined. Structural similarities between SARM1 and plant TIR domains has led our lab to demonstrate that plant TIR domains can cleave NAD+, and this activity likely plays a role in their hypersensitive response function. However, it is unclear how self-association and the cleavage event of NAD+ relates the TIR-containing NLRs to their dependence on the downstream signalling nucleo-cytoplasmic complex, EDS1 (enhanced disease suseptability 1) and its interactive partners, SAG101 (Senescence associated gene 101) and PAD4 (phytoalexin deficient 4). Through structural and molecular biological techniques I seek to understand and link plant TIR function to the EDS1 immune regulatory complex.