Cross-linking mass spectrometry: methods and applications in structural, molecular and systems biology

Over the past decade, cross-linking mass spectrometry (CLMS) has developed into a robust and flexible tool that provides medium-resolution structural information. CLMS data provide a measure of the proximity of amino acid residues and thus offer information on the folds of proteins and the topology of their complexes. Here, we highlight notable successes of this technique as well as common pipelines. Novel CLMS applications, such as in-cell cross-linking, probing conformational changes and tertiary-structure determination, are now beginning to make contributions to molecular biology and the emerging fields of structural systems biology and interactomics.