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

Zhao, H.; Szymansky, C.-M.; Lyu, X.; Huang, J.; Derbyshire, P.; Menke, F. L. H.; Webster, M. M.; Kamoun, S.; Selvaraj, M.; Jones, J. D. G.

doi:10.64898/2026.02.04.703898

bioRxiv · 10.64898/2026.02.04.703898

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

Zhao, H.·Szymansky, C.-M.·Lyu, X.·Huang, J.·Derbyshire, P.·Menke, F. L. H.·Webster, M. M.·Kamoun, S.·Selvaraj, M.·Jones, J. D. G.

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Abstract

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.

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Zhao, H., Szymansky, C.-M., Lyu, X., Huang, J., Derbyshire, P., Menke, F. L. H., Webster, M. M., Kamoun, S., Selvaraj, M., Jones, J. D. G.. 2026-02-07. Structural basis for the broad recognition specificity of an Arabidopsis immune receptor. https://doi.org/10.64898/2026.02.04.703898

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