Mass spectrometry beyond the native state

Native mass spectrometry allows the study of proteins by probing in vacuum the interactions they form in solution. It is a uniquely useful approach for structural biology and biophysics due to the high resolution of separation it affords, allowing the concomitant interrogation of multiple protein components with high mass accuracy. At its most basic, native mass spectrometry reports the mass of intact proteins and the assemblies they form in solution. However, the opportunities for more detailed characterisation are extensive, enabled by the exquisite control of ion motion that is possible in vacuum. Here we describe recent developments in mass spectrometry approaches to the structural interrogation of proteins both in, and beyond, their native state.