Summary information and primary citation

PDB-id
7x5m; SNAP-derived features in text and JSON formats; DNAproDB
Class
hydrolase-DNA
Method
cryo-EM (3.42 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.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js