Structural basis of canonical TIR-NLR activation in plant innate immunity

Maruta, N.; Gu, W.; Lim, B. Y. J.; Sorbello, M.; Ngu, D.; Jobichen, C.; Nanson, J. D.; Li, Y.; Chen, J.; Outram, M.; Bernoux, M. P.; Rahman, M. M.; Vu, T. D.; Xu, H.; Wang, L.; Kwah, K.; Burdett, H.; Mobli, M.; Ve, T.; Ellis, J. G.; Anderson, P. A.; Williams, S. J.; Dodds, P.; Kobe, B.

doi:10.64898/2026.02.03.703613

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bioRxiv · 10.64898/2026.02.03.703613

Structural basis of canonical TIR-NLR activation in plant innate immunity

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Abstract

In plants, intracellular NLRs (nucleotide-binding leucine-rich repeat receptors) detect pathogen effector proteins, form oligomeric resistosomes, and activate ETI (effector-triggered immunity). NLRs contain N-terminal signaling, central NB-ARC (nucleotide-binding) and C-terminal LRR (leucine-rich repeat) domains. NLRs with N-terminal TIR (Toll/interleukin-1 receptor) domains (TNLs) hydrolyze NAD+ (nicotinamide adenine dinucleotide) to generate signaling molecules. We determined cryo-EM structures of flax M, a canonical non C-JID (C-terminal jellyroll/Ig-like domain) TNL, in both monomeric autoinhibited conformation, and tetrameric resistosome after activation by its rust fungal effector AvrM-A. AvrM-A homodimers dissociate into monomers to bind directly to the LRR and NB-ARC domains in the M resistosome. The resistosome structure includes a non-hydrolyzable NAD+ analogue, revealing the substrate NAD+ recognition mechanism by the TIR domains. M cleaves NAD+ and generates the same signaling compounds as the related flax TNL, L6. Our findings explain the mechanism of TNL signaling, and provide a basis for rational engineering of disease-resistant crops.

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Maruta, N., Gu, W., Lim, B. Y. J., Sorbello, M., Ngu, D., Jobichen, C., Nanson, J. D., Li, Y., Chen, J., Outram, M., Bernoux, M. P., Rahman, M. M., Vu, T. D., Xu, H., Wang, L., Kwah, K., Burdett, H., Mobli, M., Ve, T., Ellis, J. G., Anderson, P. A., Williams, S. J., Dodds, P., Kobe, B.. 2026-02-06. Structural basis of canonical TIR-NLR activation in plant innate immunity. https://doi.org/10.64898/2026.02.03.703613

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