Investigating the role of protein disorder
A significant fraction of the human proteins are intrinsically disordered (IDP - intrinsically disordered proteins) and lack a well-defined 3D structure. These proteins typically fold only after recognition of a physiological partner. Although the role of disordered proteins is still to be clarified, it is hypothesized that protein disorder plays a crucial role by expanding the repertoire of protein-protein interactions taking place in the living cells. The present research project aims at clarifying the mechanisms of folding upon binding of a key experimental systems using chemical kinetics approach in synergy with protein engineering. We will therefore study the binding-induced-folding reaction of different intrinsically disordered systems, with the specific aim of clarifying the role of disorder in protein function. Moreover, we will also address the role of protein dynamics in the allosteric regulation of different protein systems.
Our major goal is therefore to unveil the role of disorder in protein recognition and to elucidate the involvement of protein frustration, in terms of energetically unfavourable interactions, in controlling allostery.