Progress in methodologies and quality-control strategies in protein cross-linking mass spectrometry

Deciphering the interaction networks and structural dynamics of proteins is pivotal to better understanding their biological functions. Cross-linking mass spectrometry (XL-MS) is a powerful and increasingly popular technology that provides information about protein-protein interactions and their structural constraints for individual proteins and multiprotein complexes on a proteome-scale. In this review, we first assess the coverage and depth of the XL-MS technique by utilizing publicly available datasets. We then delve into the progress in XL-MS experimental and computational methodologies and examine different quality-control strategies reported in the literature. Finally, we discuss the progress in XL-MS applications along with the scope for future improvements.