The receptor-like protein RXEG1 confers broad-spectrum resistance in soybean and cotton by recognizing microbial glycoside hydrolase 12 proteins.

Plants diseases cause substantial crop yield loss and threaten food security. Enhancing plant genetic resistance is a major strategy to mitigate the impact of plant diseases on agricultural production. The leucine-rich repeat receptor-like protein RXEG1 recognizes the glycoside hydrolase 12 (GH12) protein XEG1 secreted by Phytophthora sojae to mount immune responses in Nicotiana benthamiana. Here, we found that RXEG1 broadly recognizes multiple GH12 proteins of oomycete and fungal pathogens. Structural modelling and mutagenesis analyses of critical interacting residues revealed that RXEG1 binds to the enzyme-activated pocket of different GH12 proteins through an amino-terminal and a carboxy-terminal loopout region (RXEG1), forming a conserved interface with various GH12 proteins. Furthermore, the binding of RXEG1 to the active-site groove of GH12 proteins inhibits their hydrolase activity. Heterologous expression of RXEG1 in soybean and cotton confers enhanced resistance against a wide range of oomycete and fungal pathogens without growth penalties. Our data reveal that leveraging the conserved recognition and inhibition functions towards GH12 proteins enables RXEG1 application in crops to enhance resilience against various economically significant pathogens.