Mass spectrometry - from folding proteins to rotating motors

Two decades after the introduction of electrospray for the analysis of proteins the mass spectra of intact ribosomes have become almost routine. These 2.5 MDa particles remain intact during their flight through the mass spectrometer yielding new information about the stoichiometry of subcomplexes and the effects of modifications 1.
Knowledge of the intact mass of a protein or complex is only one part of the mass spectrometry information available however. Data from the disruption of protein complexes is leading to subunit interaction maps and architectural models 2. Such models are enhanced by coupling with ion mobility mass spectrometry in which the collision cross-section of a protein complex can be defined 3.
With the advent of mass spectra of membrane embedded macromolecular complexes new information and hypotheses are emerging about the effects of lipid binding 4,5. In this lecture I will trace the developments that have made possible the transition from determining the mass of an individual protein to elucidating the structures and dynamics of rotary ATPases, as well as other membrane embedded assemblies.
1 Ilag, L. L. et al. Proc Nat Acad Sci U S A 102, 8192-8197 (2005).
2 Zhou, M. et al. Proc Natl Acad Sci U S A 105, 18139-18144, (2008).
3 Ruotolo, B. T. et al. Science 310, 1658-1661 (2005).
4 Laganowsky, A. et al. Nature 510, 172-175 (2014).
5 Gupta, K. et al. Nature, 541, 421-424 (2017).