Talk Title: Studying protein structural changes on a proteome-wide scale in health and disease
After her PhD at the University of Padua (Italy) Paola Picotti joined as a postdoc the group of Ruedi Aebersold at ETH Zuerich (Switzerland), where she developed targeted proteomic techniques. In 2011, she was appointed assistant professor at ETH Zurich. Her group develops structural and chemoproteomics methods and uses them to study the consequences of intracellular protein aggregation. Paola Picotti’s research was awarded an ERC Starting grant, a Professorship grant from the Swiss National Science Foundation, the Latsis Prize, the Robert J. Cotter Award, the SGMS Award and the EMBO Young Investigator Award. Main contributions of the Picotti group are the development of a structural method to analyze protein conformational changes on a system-wide level, the discovery of novel allosteric interactions, the analysis of the determinants of proteome thermostability and the identification of a novel neuronal clearance mechanism for a protein involved in Parkinson’s disease.
Protein structural changes induced by external perturbations or internal cues can profoundly influence protein activity and thus modulate cellular physiology. Mass spectrometry (MS)-based proteomic techniques are routinely used to measure changes in protein abundance, post-translational modification and protein interactors, but much less is known about protein structural changes. In my talk, I will present a recently developed structural proteomics method that enables analysis of protein structural changes on a proteome-wide scale and directly in complex biological extracts. The approach relies on the coupling of limited proteolysis (LiP) tools and MS. LiP-MS can detect subtle alterations in secondary structure content, larger scale movements such as domain motions, and more pronounced transitions such as the switch between folded and unfolded states. I will describe how the method can be applied to the study of cellular pathways, resulting in the discovery of novel regulatory events and discuss the strength and limitations of the approach.