Our understanding of protein biochemistry is mostly based on the structure-function relationship. This approach was revolutionized by the discovery that proteins can lack a well defined three dimensional structure, while being able to exert their functions in the cellular environment. These proteins are defined as Intrinsically Disordered Proteins, or IDPs. Since the discovery of protein disorder, IDPs have been extensively studied, and for many of them a disorder-to-order transition has been reported upon binding with their natural ligands. By focusing on the interaction between the transactivation domain of the cMyb protein, a prototypical IDP, and the globular KIX domain of the CBP protein, the fundamentals of the methodology used to study binding induced folding reactions will be recapitulated, together with the biophysical approach to interpret data. In particular it will be shown that the folding pathway of cMyb is malleable and dictated by the binding partner KIX. This mechanism is called “templated folding” and we propose it to be a general folding mechanism for IDPs.
05/03/2021 Angelo Toto (Department of Biochemical Sciences (Sapienza University)