Detection and localization of protein modifications by high resolution tandem mass spectrometry

Fanyu Meng, Andrew J. Forbes, Lean M. Miller, Neil L. Kelleher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


For interrogation of peptides with diverse modifications, no other instrument is as versatile as the Fourier-transform mass spectrometer (FTMS). Particularly using electrospray ionization (ESI), many intact proteins and their proteolytic products harboring post-translational and chemical modifications (PTMs) have been studied by high resolution tandem mass spectrometry (MS/MS). The widely touted analytical figures of merit for FTMS in fact have translated into clarity when analyzing PTMs from phosphorylations to disulfides, oxidations, methylations, acetylations, and even exotic PTMs found in the biosynthesis of antibiotics and other natural products. A top down approach to PTM detection and localization is proving extensible to an increasing variety of PTMs, some of which are stable to MS/MS at the protein level but unstable to amide bond cleavage by threshold dissociations at the level of small peptides <3 kDa. In contrast, MS/MS using electron capture dissociation (ECD) allows precise localization of even labile PTMs given enough sample and abundant molecular ions. Finally, this brief synopsis of recent literature highlights specific PTMs that perturb the protein backbone therefore altering MS/MS fragmentation patterns. Thus, FTMS will continue its expansion into more laboratories in part because of its ability to detect and deconvolute the regulatory mechanisms of biology written in the language of PTMs.

Original languageEnglish (US)
Pages (from-to)126-134
Number of pages9
JournalMass Spectrometry Reviews
Issue number2
StatePublished - Mar 2005


  • FTMS
  • MS/MS
  • Post-translational modification

ASJC Scopus subject areas

  • Analytical Chemistry
  • Condensed Matter Physics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Spectroscopy


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