Ensuring food supply is of vital importance to national security and development. Nowadays, frequent outbreaks of plant diseases have led to loss of crop yield and quality, seriously threatening national food security. The application of chemical pesticides has exacerbated damage to the environment. Uncovering molecular mechanisms involved in plant immune regulations represents an important approach to solve this problem and ensure food security.
On November 8, 2024, a research article, titled "Activation of a helper NLR by plant and bacterial TIR immune signaling" by Wan Li’s team at CAS Center for Excellence in Molecular Plant Sciences (CEMPS), was published in the international academic journal Science as First Release. This research points out that both TIR-NLR immune receptors from Arabidopsis and TIR immune receptors from bacteria could generate small molecule 2’cADPR as a precursor of pRib-AMP to induce formation of immune protein complex to activate immunity and confer disease resistance. Direct application of 2’cADPR on plants is sufficient to induce immune responses and disease resistance, supporting its function as a plant immune agonist and potential to be developed as a new type of "biopesticide".
Plants express cell-surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLR) receptors, which activate pathogen associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), respectively. Both PTI and ETI work together to regulate plant disease resistance. The EDS1-PAD4-ADR1 (EPA) module plays a crucial role in PTI and ETI. NLR immune receptors containing a TIR domain act as an NAD+ hydrolase and produce small signaling molecules including pRib-AMP/ADP and 2’cADPR. How these signaling molecules regulate the EPA module and affect plant immune responses requires further investigation.
Cryo-EM structure of the EDS1-PAD4-ADR1 protein complex activated by a plant TIR reveals pRib-AMP/ADP binding to EDS-PAD4 and inducing PAD4 conformational change to allow the interaction with ADR1. TIRs generating 2’cADPR from bacteria, HopBY and AbTirTIR, also induce formation of the EPA complex and activate immunity. Analyses using high-resolution mass spectrometry and structural biology indicated that these 2’cADPR-generating TIRs also use the small molecule pRib-AMP to induce formation of EPA complex. Biochemical experiments suggested 2’cADPR could be converted into pRib-AMP in plant cells. RNAseq experiments showed that application of 2’cADPR to Arabidopsis thaliana leaves could induce ETI-like gene expression profiles and enhance their resistance to Pseudomonas syringae pv. tomato DC3000 (D36E). Given the chemical stability compared to pRib-AMP, 2’cADPR could function as a plant immune agonist and be developed into a new type of "biopesticide" to induce ETI-like broad-spectrum disease resistance in plants. Additionally, bacterial TIRs activating plant ETI immunity via 2’cADPR, suggesting cross-talks between plant and bacterial immune pathways.
The accompanying paper, from Academician Zuhua He and his collaborators published in Science also pointed out, in rice, OsTIR could use pRib-AMP to induce the formation of the rice EPA complex and enhance plant broad-spectrum disease resistance. Thes two findings collectively reveal a conserved immune mechanism across different plants, mediated by the small molecule pRib-AMP and the immune protein complex EPA.
The ETI mediated by TIRs plays an extremely important role in plant immunity and resistance breeding in agriculture. This study provides an in-depth understanding of the mechanism of TIR type of immune receptors, facilitating future rational protein engineering on TIRs. Notably, plant-derived 2’cADPR could function as a plant immune agonist and be developed into a new type of "biopesticide" to induce broad-spectrum disease resistance in plants, supporting green and sustainable development in agriculture and contributing to ensure national food security in China.
PhD candidates Hua Yu, Weiying Xu, and Sisi Chen from CEMPS are the co-first authors of the paper "Activation of a helper NLR by plant and bacterial TIR immune signaling," and Professor Li Wan is the corresponding author. This research was collaborated and supported and by Professor Zhang Yu from CEMPS. This research was funded by National Key Research and Development Program of China, Key Laboratory of Plant Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, National Natural Science Foundation of China, and Chinese Academy of Sciences Strategic Priority Research Program.
Article link: https://doi.org/10.1126/science.adr3150
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