Plant immunity is largely initiated at the cellular level, with each cell capable of autonomous detection and response, while also coordinating systemic signaling across the organism—unlike the centralized, cell-based immune system of animals.
One of the key mechanisms of plant immunity involves nucleotide-binding, leucine-rich repeat (NLR) immune receptors—intracellular receptors that detect pathogen invasion and activate a strong immune response. Unlike surface receptors, NLRs detect pathogen effector proteins that are injected by pathogens into plant cells to manipulate host biology.
NLRs are modular proteins with three main parts. They are divided into two main NLR classes—Toll/interleukin-1 receptor-like (TIR) NLRs or coiled-coil (CC) NLRs—based on the structure of their N-terminal domain.
After activation, these NLRs form multi-protein complexes—called resistosomes—that carry out the immune response. Studies have shown that certain resistosomes are pentameric (e.g., ZAR1 and Sr35), whereas others are hexameric (e.g., NRC2 and NRC4). These complexes initiate immune responses by triggering calcium (Ca 2+ ) influx into the cytoplasm. However, the G10 type of CC-NLR (CC G10 -NLR) immune receptors constitutes a unique clade among CC-NLRs and its activation mechanism has remained poorly understood.
Now, in a study published in Cell , a team led by Prof. LIU Zhiyong from the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences (CAS), along with collaborators from The Sainsbury Laboratory, the Center for Excellence in Molecular Plant Sciences of CAS, the Xianghu Laboratory (Zhejiang Provincial Agricultural Laboratory), and Zhengzhou University, has revealed a novel octameric resistosome formed by an activated wheat CC G10 -NLR immune receptor, which induces Ca 2+ influx and immune responses through a unique channel architecture.
In this study, the researchers focused on the ethyl methane sulfonate (EMS) mutant M3045 of the wheat line "Zhongke 331," which exhibits spontaneous immune phenotypes and significantly reduced agronomic traits. Although this mutation is harmful to wheat growth, it provides an opportunity to investigate immune mechanisms in wheat.
Through map-based cloning, the researchers identified the Wheat Autoimmunity 3 ( WAI3 ) gene, which encodes a CC G10 -NLR protein. Subsequent analysis revealed that a gain-of-function (GOF) single amino acid mutation in the leucine-rich repeat (LRR) domain leads to autoactivation, providing an opportunity to study the activation mechanism of CC G10 -NLR.
After expressing the WAI3 proteins in Nicotiana benthamiana , the researchers used cryo-electron microscopy to resolve the octameric structure of the activated WAI3 resistosome—marking the first time an octameric resistosome has been identified in plants.
The CC G10 -NLR WAI3 resistosome differs from known resistosomes both in the number of monomers and in its conformation, representing a novel assembly mechanism for plant NLR resistosomes.
Using Nicotiana benthamiana and animal cell expression systems, the researchers also demonstrated that the WAI3 resistosome induces Ca 2+ influx in plants but is not effective in animal cells. They hypothesized that the WAI3 resistosome may require certain unknown plant-specific factors to function—similar to NRC4, another CC-NLR.
The structure of the WAI3 resistosome also served as an important reference for studying the immune mechanism of the model plant Arabidopsis thaliana ( A. thaliana ).
Based on the octameric resistosome structure of WAI3, the researchers attempted to analyze the structure of the homologous protein RPS2 in A. thaliana . Although protein purity problems prevented the structural resolution of RPS2 via cryo-electron microscopy, the study demonstrated that activated RPS2 forms an octameric resistosome and induces Ca 2+ influx in plants, similar to WAI3.
This finding shows that the activation mechanism of CC G10 -NLR immune receptors is highly conserved in both monocotyledonous and dicotyledonous plants.
Overall, besides identifying a new octameric resistosome—WAI3—in plants, this study also shows the importance of wheat as a model for understanding plant biology in general.
Cell
An activated wheat CCG10-NLR immune receptor forms an octameric resistosome
20-Mar-2026