CRUK-UCL Centre Proteomics Seminar Series

Hosted by: Dr Silvia Surinova

Abstract

In my presentation, I will start with an overview of state of the art proteomic approaches for the quantification of proteins in complex biological and clinical samples. I will illustrate how these techniques can be used to quantify changes in protein expression on a global scale or in a targeted manner. Beyond changes in protein expression, however, biological processes can also be regulated by molecular events such as intermolecular interactions, chemical modification and conformational changes.

These events do not affect protein levels and therefore escape detection in classical proteomic screens. Reasoning that these events affect protein structure, we tested whether a global readout of protein structure could detect various types of functional alterations simultaneously. We tested this idea using a mass spectrometric approach (LiP-MS) that monitors protein structural changes in thousands of proteins simultaneously and in situ.

We showed that the structural readout, visualized as structural barcodes for each protein in a sample, captured enzyme activity changes, allosteric regulation, phosphorylation, protein aggregation and protein complex formation. It also pinpointed regulated functional sites in proteins, thus supporting the generation of mechanistic hypotheses. Coupled with protein expression changes, the structural readout dramatically increases the coverage of proteomic analyses, better links holistic and reductionist approaches, and paves the way for a new in situ structural systems biology.