Chemical cross-linking coupled to mass spectrometry was used to study two different assemblies of the human E3 ubiquitin ligase complex, GID. The 5mer complex consisted of subunits MAEA, RMND5a, TWA1, WDR26, and RanBP9; the 6mer complex consisted of the subunits of the 5mer complex and the additional subunit ARMC8β. Cross-linking experiments were performed with disuccinimidyl suberate (DSS) or pimelic dihydrazide (PDH) in combination with the coupling reagent DMTMM.