The activated plant NRC4 immune receptor forms a hexameric resistosome

Abstract Innate immune responses against microbial pathogens in both plants and animals are regulated by intracellular receptors known as Nucleotide-binding Leucine-rich Repeats (NLR) proteins. In plants, these NLRs play a crucial role in recognizing pathogen effectors, thereby initiating the activation of immune defense mechanisms. Notably, certain NLRs serve as “helper” NLR immune receptors (hNLR), working in tandem with “sensor” NLR immune receptors (sNLR) counterparts to orchestrate downstream signaling events to express disease resistance. In this study, we reconstituted and determined the cryo-EM structure of the hNLR required for cell death 4 (NRC4) resistosome. The auto-active NRC4 formed a previously unanticipated hexameric configuration, triggering immune responses associated with Ca 2+ influx into the cytosol. Furthermore, we uncovered a dodecameric state of NRC4, where the coil-coil (CC) domain is embedded within the complex, suggesting an inactive state, and expanding our understanding of the regulation of plant immune responses. One Sentence Summary The hexameric NRC4 resistosome mediates cell death associated with cytosolic Ca 2+ influx.