Exploring the structure and dynamics of macromolecular complexes by native mass spectrometry

Abstract

Mass spectrometry (MS) is an effective approach for determining the mass of biomolecules with high accuracy, sensitivity and speed. Over the past 25 years, MS performed under non-denaturing conditions (“native MS”) has been successfully exploited to investigate non-covalently associated biomolecules. Here we illustrate native MS applications aimed at studying protein-ligand interactions and structures of biomolecular assemblies, including both soluble and membrane protein complexes. Moreover, we review how the partial dissociation of holo-complexes can be used to determine the stoichiometry of subunits and their topology. We also describe “native top-down MS”, an approach based on Fourier Transform MS (FT MS), whereby non-covalent interactions are preserved while covalent bonds are selectively fragmented. Overall, native MS plays an increasingly important role in integrative structural biology, helping researchers to elucidate the three dimensional architecture of intricate macromolecular complexes.