Unusual fragmentation of Pro-Ser/Thr-containing peptides detected in collision-induced dissociation spectra

J Am Soc Mass Spectrom. 2012 Apr;23(4):602-7. doi: 10.1007/s13361-011-0216-7. Epub 2011 Aug 5.

Abstract

During collision-induced dissociation (CID)-, phosphoserine- and phosphothreonine-containing peptides frequently undergo neutral loss of phosphoric acid. Subsequent amide bond cleavage N-terminal to the site of phosphorylation results in a y ion with a mass 18 Da lower than the corresponding unmodified y fragment. We report here that when the phosphoserine or phosphothreonine is directly preceded by a proline, an unusual fragment with a mass 10 Da higher than the corresponding unmodified y ion is frequently observed. Accurate mass measurements are consistent with elimination of the phosphoric acid followed by fragmentation between the α carbon and the carbonyl group of the proline residue. We propose a cyclic oxazoline structure for this fragment. Our observation may be explained by the charge-directed S(N)2 neighboring group participation reaction proposed for the phosphoric acid elimination by Palumbo et al. [Palumbo, A. M., Tepe, J. J., Reid, G. E. Mechanistic Insights into the Multistage Gas-Phase Fragmentation Behavior of Phosphoserine- and Phosphothreonine-Containing Peptides. J. Protein Res. 7(2), 771-779 (2008)]. Considering such specific fragment ions for confirmation purposes after regular database searches may boost the confidence of peptide identifications as well as phosphorylation site assignments.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Databases, Protein
  • Molecular Sequence Data
  • Oligopeptides / chemistry*
  • Oxazoles / chemistry
  • Phosphoric Acids / chemistry
  • Phosphoserine / chemistry*
  • Phosphothreonine / chemistry*
  • Proline / chemistry*
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Tandem Mass Spectrometry

Substances

  • Oligopeptides
  • Oxazoles
  • Phosphoric Acids
  • Phosphothreonine
  • Phosphoserine
  • Proline
  • phosphoric acid