Unveiling induced folding of intrinsically disordered proteins – Protein engineering, frustration and emerging themes

Intrinsically disordered proteins (IDPs) can be generally described as a class of proteins that lack a well-defined ordered structure in isolation at physiological conditions. Upon binding to their physiological ligands, IDPs typically undergo a disorder-to-order transition, which may or may not lead to the complete folding of the IDP. In this short review, we focus on some of the key findings pertaining to the mechanisms of such induced folding. In particular, first we describe the general features of the reaction; then, we discuss some of the most remarkable findings obtained from applying protein engineering in synergy with kinetic studies to induced folding; and finally, we offer a critical view on some of the emerging themes when considering the structural heterogeneity of IDPs vis-à-vis to their inherent frustration. •Intrinsically disordered proteins (IDPs) are highly dynamic entities.•IDPs’ binding–folding reactions cooperativity make them elusive to characterization.•Templated folding is a general IDPs’ folding mechanism.•Protein frustration describes structural plasticity in IDPs’ molecular recognition.