Challenges of studying 14-3-3 protein-protein interactions with full-length protein partners

The formation of protein-complexes, or so-called protein-protein interactions (PPIs), is crucial for many physiological and pathological processes. The human interactome is estimated to contain around 130,000–650,000 different PPIs (1). Therefore, it is critical to obtain a detailed understanding of the structural characteristics and the mechanism of action of individual PPIs to acquire extended knowledge on cellular processes. Additionally, PPIs have become popular drug targets in the last two decades, as they greatly expand the druggable genome beyond classical drug targets like enzymes and receptors (1,2). This further encouraged the identification of PPIs and their role in pathological processes.