AlphaFold-guided redesign of a plant pectin methylesterase inhibitor for broad-spectrum disease resistance.

Plant cell walls are a critical site where plants and pathogens continuously struggle for physiological dominance. Here we show that dynamic remodeling of pectin methylesterification of plant cell walls is a component of the physiological and co-evolutionary struggles between hosts and pathogens. A pectin methylesterase (PsPME1) secreted by Phytophthora sojae decreases the degree of pectin methylesterification, thus synergizing with an endo-polygalacturonase (PsPG1) to weaken plant cell walls. To counter PsPME1-mediated susceptibility, a plant-derived pectin methylesterase inhibitor protein, GmPMI1, protects pectin to maintain a high methylesterification status. GmPMI1 protects plant cell walls from enzymatic degradation by inhibiting both soybean and P. sojae pectin methylesterases during infection. However, constitutive expression of GmPMI1 disrupted the trade-off between host growth and defense responses. We therefore used AlphaFold structure tools to design a modified form of GmPMI1 (GmPMI1R) that specifically targets and inhibits pectin methylesterases secreted from pathogens but not from plants. Transient expression of GmPMI1R enhanced plant resistance to oomycete and fungal pathogens. In summary, our work highlights the biochemical modification of the cell wall as an important focal point in the physiological and co-evolutionary conflict between hosts and microbes, providing an important proof of concept that AI-driven structure-based tools can accelerate the development of new strategies for plant protection.