Protein Chemistry Combined with Mass Spectrometry for Protein Structure Determination

The advent of soft-ionization mass spectrometry for biomolecules has opened up new possibilities for the structural analysis of proteins. Combining protein chemistry methods with modern mass spectrometry has led to the emergence of the distinct field of structural proteomics. Multiple protein chemistry approaches, such as surface modification, limited proteolysis, hydrogen-deuterium exchange, and cross-linking, provide diverse and often orthogonal structural information on the protein systems studied. Combining experimental data from these various structural proteomics techniques provides a more comprehensive examination of the protein structure and increases confidence in the ultimate findings. Here, we review various types of experimental data from structural proteomics approaches with an emphasis on the use of multiple complementary mass spectrometric approaches to provide experimental constraints for the solving of protein structures.