Explaining Cooperative Folding of Interacting Proteins by a Folding Superfunnel

Abstract

Generalization of the well-known folding funnel of proteins is presented here. While the polypeptide chain is treated in the frame of the conventional funnel model as an isolated object, real biological systems are considerably crowded, protein-protein interactions are fundamental phenomena during the life cycle of proteins. The generalized funnel, which we call as superfunnel represents the free energy surface of the whole system as function of the conformational coordinates of the two interacting proteins. The folding superfunnel presented here explains the folding process of interacting proteins in several specific biological processes. Three examples are presented here. The first one is the folding of a polypeptide chain with the aid of chaperones. The second important example for the protein-protein interactions is the binding assisted folding of the intrinsically disordered proteins. Binding of the intrinsically disordered protein to an ordered target protein plays a crucial role in the induced folding of the unstructured protein. The third scenario where the folding superfunnel is used is the formation of aggregates from destabilized proteins, which is an important factor in case of several conformational diseases, like Alzheimer's and Parkinson an many other ones. The folding superfunnel introduced here explains all three above cases successfully with minimal assumptions about the interaction potential.