Xiao_2025_Nature__

Plant nucleotide-binding leucine-rich repeat (NLR) receptors sense pathogen effectors and form resistosomes to confer immunity(1). Some sensor NLR resistosomes produce small molecules to induce formation of a heterotrimer complex with two lipase-like proteins, EDS1 and SAG101, and a helper NLR called NRG1 (refs. (2,3)). Activation of sensor NLR resistosomes also triggers NRG1 oligomerization and resistosome formation at the plasma membrane(4,5). We demonstrate that the Arabidopsis AtEDS1-AtSAG101-AtNRG1A heterotrimer formation is stabilized by the AtNRG1A loss-of-oligomerization mutant L134E(5,6). We report structures of AtEDS1-AtSAG101-AtNRG1A L134E and AtEDS1-AtSAG101-AtNRG1C heterotrimers with similar assembly mechanisms. AtNRG1A signalling is activated by the interaction with the AtEDS1-AtSAG101 heterodimer in complex with their small-molecule ligand. The truncated AtNRG1C maintains core interacting domains of AtNRG1A but develops further interactions with AtEDS1-AtSAG101 to outcompete AtNRG1A. Moreover, AtNRG1C lacks an N-terminal signalling domain and shows nucleocytoplasmic localization, facilitating its sequestration of AtEDS1-AtSAG101, which is also nucleocytoplasmic. Our study shows the activation and inhibition mechanisms of a plant helper NLR.