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Oligomerization of proteins and their modified forms (proteoforms) produces functional protein complexes 1, 2. Complexoforms are complexes that consist of the same set of proteins with different proteoforms 3. The ability to characterize these assemblies within cells is critical to understanding the molecular mechanisms involved in disease and to designing effective drugs. An outstanding biological question is how proteoforms drive function and oligomerization of complexoforms. However, tools to define endogenous proteoform-proteoform/ligand interactions are scarce 4. Here, we present a native top-down proteomics (nTDP) strategy that combines size-exclusion chromatography, nano liquid-chromatography in direct infusion mode, field asymmetric ion mobility spectrometry, and multistage mass spectrometry to identify protein assemblies (≤ 70 kDa) in breast cancer cells and in cells that overexpress EGFR, a …