Kings College London 1 article published in JoVE Biology Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies Caroline Haupt*1, Tommy Hofmann*1, Sabine Wittig*1, Susann Kostmann1, Argyris Politis2, Carla Schmidt1 1Interdisciplinary research center HALOmem, Martin Luther University Halle-Wittenberg, 2Department of Chemistry, Kings College London The architecture of protein complexes is essential for their function. Combining various mass spectrometric techniques proved powerful to study their assembly. We provide protocols for chemical cross-linking and native mass spectrometry and show how these complementary techniques help to elucidate the architecture of multi-subunit protein assemblies.