Structure-guided insights into PERU-mediated recognition of Phytophthora infestans in potato

Late blight, caused by the oomycete Phytophthora infestans, remains a persistent threat to global potato production. Resistance breeding primarily relies on the introgression of intracellular immune receptors, which are often rapidly overcome due to the pathogen’s high evolutionary potential. In contrast, Pattern Recognition Receptors (PRRs) at the cell surface are expected to confer more durable resistance, because they detect conserved pathogen molecules. In this study, we focus on the PRR PERU in potato, which recognizes transglutaminase-derived Pep-13/25 peptides from P. infestans. Both PERU and Pep-13/25 exhibit genetic diversity in wild Solanum species and P. infestans strains, respectively, resulting in distinct recognition specificities. This natural diversity provides an opportunity to dissect key determinants of ligand perception, co-receptor interactions and potential effector-mediated suppression. Using AlphaFold3 (AF3)-based structural modelling, we identified candidate residues at the PERU-Pep-13/25 interface involved in recognition. Mutating these residues in PERU showed a strong reduction in recognition compared to wild-type PERU. By combining co-evolutionary analysis, AF3-guided structure predictions and functional assays in potato, we define the molecular determinants of Pep-13/25 perception by PERU, bringing us closer to structure-guided design of surface receptors for durable resistance against P. infestans.