Summary information and primary citation
- PDB-id
- 7x5l; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- hydrolase-DNA
- Method
- cryo-EM (3.51 Å)
- Summary
- Tir-dsDNA complex, the initial binding state
- Reference
- Yu D, Song W, Tan EYJ, Liu L, Cao Y, Jirschitzka J, Li E, Logemann E, Xu C, Huang S, Jia A, Chang X, Han Z, Wu B, Schulze-Lefert P, Chai J (2022): "TIR domains of plant immune receptors are 2',3'-cAMP/cGMP synthetases mediating cell death." Cell, 185, 2370-2386.e18. doi: 10.1016/j.cell.2022.04.032.
- Abstract
- 2',3'-cAMP is a positional isomer of the well-established second messenger 3',5'-cAMP, but little is known about the biology of this noncanonical cyclic nucleotide monophosphate (cNMP). Toll/interleukin-1 receptor (TIR) domains of nucleotide-binding leucine-rich repeat (NLR) immune receptors have the NADase function necessary but insufficient to activate plant immune responses. Here, we show that plant TIR proteins, besides being NADases, act as 2',3'-cAMP/cGMP synthetases by hydrolyzing RNA/DNA. Structural data show that a TIR domain adopts distinct oligomers with mutually exclusive NADase and synthetase activity. Mutations specifically disrupting the synthetase activity abrogate TIR-mediated cell death in Nicotiana benthamiana (Nb), supporting an important role for these cNMPs in TIR signaling. Furthermore, the Arabidopsis negative regulator of TIR-NLR signaling, NUDT7, displays 2',3'-cAMP/cGMP but not 3',5'-cAMP/cGMP phosphodiesterase activity and suppresses cell death activity of TIRs in Nb. Our study identifies a family of 2',3'-cAMP/cGMP synthetases and establishes a critical role for them in plant immune responses.
