Chemical cross-linking in the structural analysis of protein assemblies

•Chemical cross-linking and mass spectrometry (CXMS) reveals residues in spatial proximity.•When used at low concentrations, cross-linkers do not substantially alter protein structures.•CXMS analysis is fast, sensitive, robust and compatible with other in vitro and in vivo methods.•Quantitative CXMS analysis elucidates conformational changes and equilibria of proteins.