Two distinct modes of action of molecular glues in the plant hormone co-receptor COI1-JAZ system

The plant hormone (3R, 7S)-jasmonoyl-L-isoleucine ((3R, 7S)-JA-Ile) is perceived by the COI1-JAZ co -receptor in Arabidopsis thaliana, leading to the activation of gene expression for plant defense responses, growth, development, and other processes. Therefore, understanding the interaction between the COI1-JAZ co-receptor and its ligands is essential for the development of COI1-JAZ agonists and antagonists as potent chemical tools for regulating (3R, 7S)-JA-Ile signaling. This study demonstrated that COI1JAZ has two independent modes of ligand perception using a differential scanning fluorimetry (DSF) assay. (3R, 7S)-JA-Ile is perceived through a one-step model in which (3R, 7S)-JA-Ile causes protein- protein interaction between COI1 and JAZ. In contrast, coronatine (COR), a mimic of (3R, 7S)-JA-Ile, is perceived through a two-step model in which COR is first perceived by COI1 and then recruits JAZ to form the COI1-COR-JAZ complex. Our results demonstrate two distinct modes of action of molecular glues causing protein-protein interactions.