TIR domains of plant immune receptors are 2',3'-cAMP/cGMP synthetases mediating cell death

Yu, D.; Song, W.; Tan, E. Y. J.; 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.

doi:10.1101/2021.11.09.467869

bioRxiv · 10.1101/2021.11.09.467869

TIR domains of plant immune receptors are 2',3'-cAMP/cGMP synthetases mediating cell death

Yu, D.·Song, W.·Tan, E. Y. J.·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.

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Abstract

2',3'-cAMP is a positional isomer of the well-established second messenger 3',5'-cAMP, but little is known on 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 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 shows that a TIR domain adopts distinct oligomers with dual and exclusive enzymatic activity. Mutations specifically disrupting the synthetase activity abrogate TIR-mediated cell death in Nicotiana benthamiana, 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 N. benthamiana. Our study identifies a novel family of 2',3'-cAMP/cGMP synthetase and establishes a role for the noncanonical cNMPs in plant immune responses.

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Yu, D., Song, W., Tan, E. Y. J., 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.. 2021-11-10. TIR domains of plant immune receptors are 2',3'-cAMP/cGMP synthetases mediating cell death. https://doi.org/10.1101/2021.11.09.467869

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