Towards integrative structural mass spectrometry: Benefits from hybrid approaches

Structural mass spectrometry encompasses an increasing range of methods aimed at collecting as much structural information as possible on a biomolecule or its related complexes. Originally limited to the analysis of the primary structures of proteins, mass spectrometry has evolved over the past 20 years to provide information on the secondary, tertiary and even quaternary structure of proteins. Furthermore, the systems investigated with these methods have become more and more complex, as many developments have progressively overcome the main challenges of the size, heterogeneity, and/or solubility of protein complexes. A decade ago, most of these techniques were still the playground of a handful of specialists. However, the potential of these methods and their complementarity to other classical biophysical methods have driven an increasing number of users to develop new techniques and, perhaps more crucially, manufacturers have developed improved instruments and solutions/kits that are now commercially available. Today, more and more groups are combining structural proteomics techniques in order to gain additional information, as we will see in this review. This article will particularly focus on the analysis of peptides and protein complexes. First, the main methods of structural proteomics will be described. Then different possible combinations will be described, including how complementary they are, what synergistic information can be obtained from them, and what their current limitations are.