HMA proteins produce 2′,3′-cNMP signaling molecules and activate CNL-mediated immunity in rice

SUMMARY Plants deploy a sensor repertoire, usually NLRs, to perceive pathogen effectors and activate executor NLR-triggered immunity. Here we reveal that rice HMA proteins function as sensors detecting the Magnaporthe oryzae MAX effector AvrPigm to trigger broad-spectrum blast resistance mediated by the CNL PigmR. AvrPigm is conserved with multiple copies in blast genomes and targets HMA proteins, facilitating HMA translocation into the cytoplasm. Cryo-EM structure of the HPP04 HMA reveals a filament-like oligomer with ssDNA/RNA bound inside the filament, which display cyclic nucleotide synthase activity to generate 2′,3′-cNMP in a CNL-dependent manner. We further discovered that the LRR domains of the executor CNLs perceive 2′,3′-cNMP to mount immunity. Our study thus establishes an unrecognized immunity mode with a distinct repertoire of sensor receptors that produce signaling molecules that are perceived by the LRR domains of executor NLRs to mediate immunity, shedding new light on the sensor-executor conception and immune activation in plants. Highlights HMA proteins and CNL receptors form a new sensor-executor mode in plant immunity Cryo-EM reveals the filament-like structure of HMA-ssRNA/ssDNA HMA proteins are cyclic nucleotide synthetases to generate 2′,3′-cNMP LRR domains of CNLs perceive 2′,3′-cNMP to mediate immunity