Structural basis for the broad recognition specificity of an Arabidopsis immune receptor

Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors typically confer resistance through recognition of specific pathogen effectors. The Arabidopsis NLR WRR4A defies this paradigm by recognizing multiple sequence-divergent effectors from Albugo candida, conferring resistance to multiple pathogen races. Despite minimal sequence similarity, these effectors share a conserved N-terminal ferredoxin-like fold. Through cryo-EM structure determination of two WRR4A resistosomes bound to sequence-distinct effectors, combined with AlphaFold modelling, we reveal a shape-based recognition mechanism: WRR4A engages structurally conserved backbone features of the effectors in a mostly side chain-independent manner, enabling recognition of diverse effectors with similar three-dimensional architectures. These insights guided successful engineering of WRR4A to acquire novel recognition specificity. In addition, analysis of the monomeric WRR4A resting state reveals a distinct domain architecture characteristic of C-JID-containing TIR-NLRs and informs their activation mechanism. This work provides insights into NLR-mediated broad-spectrum recognition and the potential for structure-informed engineering of improved crop resistance.