{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang S"],"funding":["Universität Zürich (University of Zurich)","Universität Zürich","Zurich-Basel Plant Science Center"],"pagination":["1642-1657"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12364711"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(8)"],"pubmed_abstract":["In the ongoing plant-pathogen arms race, plants use pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs), while in successful pathogens, PAMPs can evolve to evade detection. Engineering PRRs to recognize evading PAMPs could potentially generate broad-spectrum and durable disease resistance. Here we reverse-engineered two natural variants of the PRR FLAGELLIN SENSING 2 (FLS2), VrFLS2XL and GmFLS2b, with extended recognition specificities towards evading flg22 variants. We identified minimal gain-of-function residues enabling blind FLS2s to recognize otherwise evading flg22 variants. We uncovered two strategies: (1) optimizing FLS2-flg22 interaction around flg22's key evasion sites and (2) strengthening direct FLS2-BAK1 interaction to overcome weak agonistic and antagonistic flg22s, respectively. In addition, we leveraged polymorphisms that enhance recognition through unknown mechanisms to engineer a superior recognition capability. These findings offer basic design principles to engineer PRRs with broader recognition spectra, paving the way for PRR engineering to generate precisely gene-edited disease-resistant crops."],"journal":["Nature plants"],"pubmed_title":["Reverse engineering of the pattern recognition receptor FLS2 reveals key design principles of broader recognition spectra against evading flg22 epitopes."],"pmcid":["PMC12364711"],"funding_grant_id":["n/a"],"pubmed_authors":["Kim G","Bender KW","Liu S","Caflisch A","Zhang S","Zipfel C","Lai HF"],"additional_accession":[]},"is_claimable":false,"name":"Reverse engineering of the pattern recognition receptor FLS2 reveals key design principles of broader recognition spectra against evading flg22 epitopes.","description":"In the ongoing plant-pathogen arms race, plants use pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs), while in successful pathogens, PAMPs can evolve to evade detection. Engineering PRRs to recognize evading PAMPs could potentially generate broad-spectrum and durable disease resistance. Here we reverse-engineered two natural variants of the PRR FLAGELLIN SENSING 2 (FLS2), VrFLS2XL and GmFLS2b, with extended recognition specificities towards evading flg22 variants. We identified minimal gain-of-function residues enabling blind FLS2s to recognize otherwise evading flg22 variants. We uncovered two strategies: (1) optimizing FLS2-flg22 interaction around flg22's key evasion sites and (2) strengthening direct FLS2-BAK1 interaction to overcome weak agonistic and antagonistic flg22s, respectively. In addition, we leveraged polymorphisms that enhance recognition through unknown mechanisms to engineer a superior recognition capability. These findings offer basic design principles to engineer PRRs with broader recognition spectra, paving the way for PRR engineering to generate precisely gene-edited disease-resistant crops.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-02T03:46:56.255Z","creation":"2026-04-07T17:36:06.709Z"},"accession":"S-EPMC12364711","cross_references":{"pubmed":["40721668"],"doi":["10.1038/s41477-025-02050-5"]}}