Nature Research Webinar: 3D Proteome Snapshots Enable High-resolution Functional Proteomics Screens

Proteomics is routinely applied to detect changes in protein levels in response to perturbations and to pinpoint altered biological processes. Beyond protein expression changes, however, biological processes are also regulated by events such as intermolecular interactions, post translational modification and conformational changes. These events do not necessarily alter protein levels and typically escape detection in classical protein expression screens.

This webcast presents how a global readout of protein structure can detect various types of protein functional alterations concomitantly, promising to drastically expand the coverage and resolution of functional proteomics screens. The approach, relying on the Limited Proteolysis Mass Spectrometry (LiP-MS) technique, monitors structural changes in thousands of proteins simultaneously in situ. It captures allosteric regulation, phosphorylation, protein complex formation, enzyme activity changes, protein aggregation and altered protein levels within the same analysis, thus substantially expanding the coverage of proteomic screens. Further, it pinpoints altered functional sites on proteins, thus supporting the generation of mechanistic hypotheses at high throughput. Applications of this approach include the study of complex phenotypes and biological mechanisms, the identification of disease biomarkers, drug target deconvolution and analysis of drug mechanism of action.