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Poster

Session: Session 1 Presenting Authors at Posters (Evens)

P-082 - Structural basis for broad-spectrum recognition and activation of an Arabidopsis TIR-NLR

Tuesday, July 15, 2025
09:55 - 11:30  
Location: Confex Hall 3
Extracellular & Intracellular non-self recognition & signaling
Abstract Text: The TIR-NLR immune receptor WRR4A from Arabidopsis provides resistance against multiple races of the white rust pathogen Albugo candida by recognizing diverse CCG effectors, despite their low sequence identity. Understanding this broad recognition mechanism could facilitate engineering durable disease resistance in crops. Using single-particle Cryo-EM, we resolved 3D structures of WRR4A in complex with two distinct CCG effectors, revealing a tetrameric "four-leaf clover" architecture where effectors bind to the LRR and C-JID domains through conserved interfaces. Structural analysis showed that WRR4A primarily interacts with effector backbone atoms through side-chain bonds, enabling recognition of structurally similar but sequence-divergent effectors. AlphaFold-multimer predictions accurately distinguished recognized from unrecognized CCGs and guided successful engineering of WRR4A variants with expanded recognition specificity. Additionally, we obtained the EM structure of monomeric WRR4A in its resting state. Comparison with effector-bound structures revealed dramatic domain rearrangements during activation. This work advances our understanding of both recognition and activation mechanisms of plant TIR-NLRs, providing new opportunities for engineering broad-spectrum disease resistance in crops.