Differential binding of salicylic acid, phenolic acid derivatives and co- factors determines the roles of Arabidopsis NPR1 to NPR4 in plant immunity

SummaryO_LIGenetic studies have demonstrated that NPR1 is the key positive regulator of salicylic acid (SA)-induced PR-1 gene induction and systemic acquired resistance (SAR). In Arabidopsis, family members NPR1 to NPR4 share domain architecture. C_LIO_LIYeast hybrid assays were used to explore biochemical capabilities of NPR1 to NPR4. C_LIO_LIAll NPR1 to NPR4 are responsive to SA. SA perception proceeds via the conserved arginine embedded in a C-terminal LENRV-like motif. Clade 2 proteins NPR3 and NPR4 perceive SA directly, while clade 1 members NPR1 and NPR2 require interaction with partner proteins NIMIN1/NIMIN2 and TGA factors, respectively, to enable SA sensing. Intriguingly, NPR3 is considerably more sensitive to the synthetic analog 3,5-dichloroanthranilic acid than to SA, and all NPR1 to NPR4 are able to sense the microbial metabolite 6-methyl SA. C_LIO_LIWe suggest that the plant{acute}s ability to track SA and phenolic acid derivatives through NPR proteins has evolved to support diverse defense signaling outputs that are activated in parallel by agonists which may be of microbial or plant origin. In this line, NPR1-NIMIN2/NIMIN1 complex is the prime receptor for SA synthesized by plants in response to microbial attack, while NPR3 induces defense different from SAR primarily via unrecognized signal molecules. C_LI