Revealing Higher Order Protein Structure Using Mass Spectrometry

J Am Soc Mass Spectrom. 2016 Jun;27(6):952-65. doi: 10.1007/s13361-016-1385-1. Epub 2016 Apr 14.


The development of rapid, sensitive, and accurate mass spectrometric methods for measuring peptides, proteins, and even intact protein assemblies has made mass spectrometry (MS) an extraordinarily enabling tool for structural biology. Here, we provide a personal perspective of the increasingly useful role that mass spectrometric techniques are exerting during the elucidation of higher order protein structures. Areas covered in this brief perspective include MS as an enabling tool for the high resolution structural biologist, for compositional analysis of endogenous protein complexes, for stoichiometry determination, as well as for integrated approaches for the structural elucidation of protein complexes. We conclude with a vision for the future role of MS-based techniques in the development of a multi-scale molecular microscope. Graphical Abstract ᅟ.

Keywords: Electrospray ionization; Endogenous protein complexes; Folding state in solution; Higher order structure; MALDI; Mass spectrometry; Molecular microscope; Native mass spectrometry; Protein assembly; Protein complex; Protein composition; Stoichiometry; Structural biology; X-ray crystallography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Mass Spectrometry*
  • Peptides
  • Proteins / chemistry*
  • Spectrometry, Mass, Electrospray Ionization


  • Peptides
  • Proteins