A conformation-specific approach to native top-down mass spectrometry

Native top-down mass spectrometry is a powerful approach for analyzing proteoforms, but one which largely disregards protein conformation. We report a new ion mobility-enabled method for performing native top-down MS in a conformation-specific manner. Our approach identified conformation-linked differences in backbone dissociation which simulta-neously inform upon proteoform variations and provide structural insights. We also illustrate that our method can be applied to protein-ligand complexes, either to identify components or to probe ligand-induced structural changes.