Significance Most proteins carry out their function by associating with other proteins in stable or transient complexes. Structural analysis of such complexes, for example by crystallography, is frequently performed to study their function or mode of action. However, many large complexes are refractory to traditional structural biology methods. Alternative methods have been developed that are often combined with computational methods in hybrid structural biology strategies. Among these, the combination of chemical cross-linking and MS (XL-MS) has shown to be particularly informative. Current XL-MS methods mainly rely on the coupling of lysine residues. Here we describe a chemistry to cross-link acidic residues that generates structural information complementary to that obtained by amine-specific cross-linking, thus significantly expanding the scope of XL-MS analyses.