Ricerc@Sapienza

The dogma of structure-function relationship in protein biophysics has recently been challenged by the striking discovery of many natively unfolded proteins in the human proteome and the concept of functional disorder is revolutionary for scientific community. The characterization of intrinsically unstructured proteins has been, to date, particulary elusive because of their heterogeneous nature.
The aim of this research project is the study of disorder on some selected model system to exemplify both the local and global disorder.
In this context, the binding induced folding of intrinsically disordered systems will be investigated either in protein-protein or protein-DNA interactions. The systems selected are: i) the PDZ domain family, a class of fully native domains displaying frustrated clusters located in the functional sites; ii) the PH domain, a peculiar class of split proteins, whose folding is triggered by the recognition of two complementary halves; iii) Ets domain of SAP-1, a transcription factor whose disorder and flexibility have been suggested to be critical to scan the DNA superstructure.
These systems will be extensively characterized through protein engineering, kinetic and thermodynamic studies.