The Structural Mass Spectrometry and Proteomics Unit was created late 2012. Since the 1st of January 2017, it is a mixed Institut Pasteur/CNRS Unit of Service and Research (USR2000 MSBio, Mass Spectrometry for Biology). The Unit includes a research group, dedicated to the development of structural proteomics (top-down proteomics, cross-linking combined to MS, native MS and HX MS) and a proteomics platform (bottom-up proteomics). The Unit is also part of the CITECH.
Top-down proteomics is an emerging technology based on the analysis of intact proteins using very high-resolution mass spectrometry. It provides the highest molecular precision for analyzing primary structures and determining post-translational modifications by examining proteins in their intact state, leading to more straightforward and reliable results than the classical bottom-up approach based on protein enzymatic digestion. Top-down proteomics holds great promise in clinical research and in particular in clinical microbiology, a major research axis of the unit.
Cross-linking combined to mass spectrometry is a powerful approach to address both the structure and composition of protein complexes. To improve the crucial stage of detection and characterisation of cross-linked peptides, we have developed a new generation of cross-linking agents based on click-chemistry.
Native MS allows the structural investigation of protein complexes with the sensitivity, speed, unlimited mass range and accuracy of mass spectrometry. The exact mass of the proteins can be obtained, as well as the stoichiometry of the assembly, its conformation and topological arrangement of the subunits within the complex.
HDX (Hydrogen Deuterium Exchange) MS is based on the different exchange rates of hydrogens in proteins. Exchange rates are a function of solvent accessibility and hydrogen bonding. HX MS can be used to monitor conformational changes in proteins, characterize protein folding pathways or protein-protein interactions.