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Poster

Session: Session 1 Presenting Authors at Posters (Evens)

P-080 - Structural and computational investigation of LORE receptor binding specificity to medium chain 3-hydroxylated fatty acids

Tuesday, July 15, 2025
09:55 - 11:30  
Location: Confex Hall 3
Extracellular & Intracellular non-self recognition & signaling

    Presenting Author(s)

  • FY

    Fan-Yu Yu

    PhD Student
    Department of Biology, University of Fribourg
    Fribourg, Fribourg, Switzerland

    • Author(s)

  • LS

    Lin-Jie Shu

    University of Fribourg
    Wako, Saitama, Japan

  • AN

    Alessandro Nicoli

    Leibniz-LSB@TUM
    Freising, Bayern, Germany

  • AD

    Antonella Di Pizio

    Leibniz-LSB@TUM
    Freising, Bayern, Germany

  • SR

    Stefanie Ranf

    Professor
    University of Fribourg
    Fribourg, Fribourg, Switzerland

LORE (LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION or SD1-29) is a plasma membrane-localized pattern recognition receptor in Brassicaceae. Immune signaling of LORE is triggered upon sensing medium-chain 3-hydroxylated fatty acids (mc-3-OH-FAs) with a chain length of 8-12 carbons in the extracellular domain (ECD). As a member of the S-domain receptor kinase family, the ECD of LORE comprises two lectin-like domains, an epidermal growth factor-like domain, and a plasminogen-apple-nematode domain. This project aims to unravel the activation mechanism by investigating the ligand binding mode of LORE with experimental and computational approaches. Here, we show that the LORE ligand-binding pocket is located in the second lectin-like domain by ECD swapping with a 3-OH-FA non-binding ortholog, and molecular dynamic analysis (in collaboration with Antonella Di Pizio’s group, Leibniz-LSB@TUM). Mutating conserved residues or a key polar residue in the predicted binding pocket disrupts ligand binding of LORE and, thus, mc-3-OH-FA-induced immune signaling. Recent molecular dynamics modeling with 3-hydroxy-C10:0 fatty acid has provided insights into the ligand’s potential entry point and mode of binding. This will deepen our understanding of how chain-length-specific sensing of mc-3-OH-FAs occurs and how ligand binding ultimately activates LORE and downstream signaling.