TIR Domains Flashcards
What does TIR stand for?
Toll/interleukin-1 receptor.
What are the function of TIR domains in plants?
In plants, TIR domains are part of intracellular NOD-like receptors (NLRs). TIR domains also act as 2’, 3’-cAMP/cGMP synthetases by hydrolysing DNA/RNA. Both the NADase and synthetase activity of TIR domain proteins is necessary for their cell death activity.
Explain how recognition of effector proteins by NLR receptors leads to a hypersensitive response in plants.
Intracellular NLR receptors recognise pathogen effectors. When they recognise an effector, they induce oligomeric NLR complexes called resistosomes. Activation of NLR resistosomes induces effector-triggered immunity (ETI), often including a hypersensitive response (HR). The TIR-NLR (TNLs) resistosomes function as holoenzymes of TIR-encoded NADase. The NADase activity is required for the activation of two immune signalling nodes, EDS1-SAG101 and EDS1-PAD4 heterodimers, and the helper NLRs (RNLs), NRG1s, and ADR1s. Once TNLs are activated, EDS1-SAG101 forms a hetero complex with NRG1s and EDS1-PAD4 forms a hetero complex with ADR1s, inducing Ca2+-channel activity of the RNLs. This then leads to cell death and disease resistance.
Where can TIR be found in the tree of life, and how do they work in this particular group?
In plants, TIR domains are present in intracellular NLR receptors. These TIR domains have an NADase function and act as 2’, 3’-cAMP/cGMP synthetases by hydrolysing DNA/RNA. Both the NADase and synthetase activity of TIR domain proteins is necessary for their cell death activity.
In animals, TIR domains are found in Toll and Toll-like receptors (TLRs), their cytosolic adaptor proteins, and the interleukin-1 receptor (IL-1R) family. In animals, TIR domains recruit intracellular signalling complexes, mediating inflammatory responses and/or cell death. By contrast, the human SARM1 protein, which contains a TIR domain, functions as an NADase.
In bacteria, TIR domains can be found in an anti-phage resistance mechanism called Thoeris, that functions as an NADase to generate immune signals, resulting to cell death.
