Ricerc@Sapienza

Despite over 75% of the eukaryotic proteome is composed by multi-domain proteins, much of our current knowledge on protein folding relies on studies on single domain proteins. In fact, protein domains are generally assumed to be able to fold independently, as proven by the possibility to express them in isolation. However, it cannot be excluded that the interaction between these structural subunits may play a critical role in the formation of the native structure, as well as in dictating misfolding events. Consequently, recent years have seen a considerable growing effort in developing methods to understand the folding of more complex multi-domain systems.
The present project is about the description of the folding mechanism of a multi-domain tandem construct, comprising two distinct covalently bound PDZ domains, belonging to a protein called Whirlin, a scaffolding protein of the hearing apparatus.
To exercise its biological function, Whirlin undergoes a mechanical process of unfolding/refolding, making this protein a suitable system for the studying of the role of multi-domain assembly in protein folding mechanisms.