A sunflower FLS2 guides reconstruction of recognition of a Xanthomonas flg22 escape variant across divergent FLS2 receptors
- 1Nanjing Forestry University
Abstract
FLS2-mediated perception of the bacterial flagellin epitope flg22 is frequently compromised by pathogen sequence variation, and Val14-containing Xanthomonas flg22 variants remain unrecognized by multiple characterized expanded-recognition FLS2 homologues. Using AlphaFold 3-based structural screening of 256 natural FLS2 homologues against the flg22 epitope from Xanthomonas campestris pv. campestris (flg22Xcc), we identified sunflower HaFLS2-1 as the top structural candidate and experimentally validated its recognition through biochemical and immune-response assays. We then used ligand-proximal HaFLS2-1 residue states as a donor reference for iterative engineering of divergent FLS2 homologues from two distinct plant families, PsFLS2 and TjFLS2. Distinct recipient-specific residue solutions emerged in the two backgrounds, and representative functional variants carrying ten or fewer amino-acid substitutions acquired flg22Xcc recognition. Together, these results show that, for this defined flg22Xcc escape challenge, AF3-guided discovery and iterative local sequence exploration can reconstruct recognition across divergent FLS2 scaffolds through a limited number of receptor substitutions.
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BibTeX
@misc{zhong2026sunflower,
title = {{A sunflower FLS2 guides reconstruction of recognition of a Xanthomonas flg22 escape variant across divergent FLS2 receptors}},
author = {L. Zhong and L. Wu and Q. Cheng},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.757162},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757162v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A sunflower FLS2 guides reconstruction of recognition of a Xanthomonas flg22 escape variant across divergent FLS2 receptors
AU - L. Zhong
AU - L. Wu
AU - Q. Cheng
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.757162
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.757162v1
AB - FLS2-mediated perception of the bacterial flagellin epitope flg22 is frequently compromised by pathogen sequence variation, and Val14-containing Xanthomonas flg22 variants remain unrecognized by multiple characterized expanded-recognition FLS2 homologues. Using AlphaFold 3-based structural screening of 256 natural FLS2 homologues against the flg22 epitope from Xanthomonas campestris pv. campestris (flg22Xcc), we identified sunflower HaFLS2-1 as the top structural candidate and experimentally validated its recognition through biochemical and immune-response assays. We then used ligand-proximal HaFLS2-1 residue states as a donor reference for iterative engineering of divergent FLS2 homologues from two distinct plant families, PsFLS2 and TjFLS2. Distinct recipient-specific residue solutions emerged in the two backgrounds, and representative functional variants carrying ten or fewer amino-acid substitutions acquired flg22Xcc recognition. Together, these results show that, for this defined flg22Xcc escape challenge, AF3-guided discovery and iterative local sequence exploration can reconstruct recognition across divergent FLS2 scaffolds through a limited number of receptor substitutions.
ER -