The role and structure of molecular glues in plant signalling networks

Protein-protein interactions are one of the pillars of all life processes. Many signalling molecules work by promoting and stabilizing these interactions. These molecular 'glues' bind simultaneously to two proteins inducing their interaction, which would be otherwise less favourable or non-favourable. Importantly, they can be harnessed for a clinical purpose, but, despite advances in medicine, the wealth of natural molecular glues in plants have only rarely been commercially utilized. These molecular glues may be plant-endogenous or plant-exogenous small molecules or peptides, and they may be involved in many different processes, such as growth promotion or stress response, opening new opportunities for crop protection, along with other applications. In this Review, we analyse the underlying structural motives and molecular interactions in detail, classifying the modes of actions based on their nature (small ligands versus peptides) and receptor classes. We discuss both natural metabolites and mimetics of such compounds, highlighting similarities and differences between signalling pathways and comparing them with relevant mechanisms in mammals.