Profiling Protein-Protein Interactions and Protein Structures Using Chemical Cross-linking and Mass Spectrometry

Protein cross-linking strategies coupled to mass spectrometry is a powerful tool for studying protein structures, protein surface topologies and protein-protein interactions. There are more than one hundred chemical crosslinkers, and some of them are already commercially available. However, the current researches require new and more effective crosslinkers and more intelligent data analysis software tools. Here, we describe some new features of crosslinkers such as cleavable cross-linkers that facilitate detection by mass spectrometry, affinity crosslinkers using click-chemistry that facilitate separation and enrichment of cross-linked peptides, and crosslinkers with the combined features. In addition, the evolution in software remarkably improves the data analysis efficiency and makes it possible to perform large-scale identification of cross-linked peptides. The advances in protein cross-linking analysis software are also addressed.