Reprogramming of flagellin receptor responses with surrogate ligands.

Area of Science:

• Plant molecular biology
• Plant immunity
• Receptor kinase signaling

Background:

• Receptor kinases (RKs) are crucial for plant cellular processes, responding to various external signals.
• The ability of individual plant RKs to perceive structurally diverse ligands is largely unknown.
• FLAGELLIN-SENSING 2 (FLS2) is a well-characterized RK that recognizes bacterial flagellin peptides to initiate plant defense.

Purpose of the Study:

• To investigate if plant RKs can process signals from distinct types of ligands.
• To identify novel ligands for the FLS2 receptor.
• To explore the signaling flexibility of RKs using chemical probes.

Main Methods:

• A large-scale reverse chemical screen was employed to test over 20,000 small molecules for interaction with the FLS2 sensory domain.
• Functional assays were conducted to assess the impact of identified small molecules on FLS2 activity and downstream responses.
• Analysis of gene expression programs triggered by these novel interactions.

Main Results:

• Two small molecules were identified that interact with the FLS2 receptor in an atypical manner.
• These surrogate ligands weakly activate FLS2, leading to a functional antibacterial response.
• The activation by small molecules induced unusual gene expression patterns, distinct from flagellin-induced immunity.

Conclusions:

• Individual plant RKs, like FLS2, exhibit a greater degree of ligand-binding flexibility than previously understood.
• Biased ligand interactions with RKs can uncover novel signaling pathways and cellular outputs.
• Chemical probes acting as biased ligands are valuable tools for dissecting complex RK signal transduction.