Neutral Loss of Isocyanic Acid in Peptide CID Spectra: A Novel Diagnostic Marker for Mass Spectrometric Identification of Protein Citrullination

Gang Hao, Danchen Wang, Jane Gu, Qiuying Shen, Steven S. Gross, Yanming Wang

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Protein citrullination is emerging as an important signaling mechanism that modulates a variety of biological processes. This protein modification constitutes only a 1 Da mass shift, and can be readily confused with other common protein modifications that yield an identical mass shift. In an attempt to develop a robust methodology for detection of protein citrullination sites, we analyzed synthetic citrulline-containing peptides by electrospray ionization tandem mass spectrometry. Collision-induced dissociation (CID) spectra revealed abundant neutral loss of 43 Da from citrullinated peptide precursor ions, which was reconciled by elimination of the HNCO moiety (isocyanic acid) from the citrulline ureido group. The elimination occurs readily in multiple charge states of precursor ions and also in b and y ions. HNCO loss in CID spectra provides a novel diagnostic marker for citrullination, and its utility was demonstrated by the discovery of Arg197 as the specific site of citrullination on nucleophosmin upon peptidylarginine deiminase 4 treatment.

Original languageEnglish (US)
Pages (from-to)723-727
Number of pages5
JournalJournal of the American Society for Mass Spectrometry
Volume20
Issue number4
DOIs
StatePublished - Apr 2009

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Spectroscopy

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