Ligand-triggered allosteric ADP release primes a plant NLR complex

Pathogen recognition by nucleotide-binding (NB), leucine-rich repeat (LRR) receptors (NLRs) plays roles in plant immunity. The pv. effector AvrAC uridylylates the PBL2 kinase, and the latter (PBL2 ) acts as a ligand to activate the NLR ZAR1 precomplexed with the RKS1 pseudokinase. Here we report the cryo-electron microscopy structures of ZAR1-RKS1 and ZAR1-RKS1-PBL2 in an inactive and intermediate state, respectively. The ZAR1 domain, compared with animal NLR domains, is differently positioned to sequester ZAR1 in an inactive state. Recognition of PBL2 is exclusively through RKS1, which interacts with ZAR1 PBL2 binding stabilizes the RKS1 activation segment, which sterically blocks ZAR1 adenosine diphosphate (ADP) binding. This engenders a more flexible NB domain without conformational changes in the other ZAR1 domains. Our study provides a structural template for understanding plant NLRs.