Mobile and localized protons: A framework for understanding peptide dissociation

Vicki H. Wysocki, George Tsaprailis, Lori L. Smith, Linda A. Breci

Research output: Contribution to journalReview articlepeer-review

897 Scopus citations


Protein identification and peptide sequencing by tandem mass spectrometry requires knowledge of how peptides fragment in the gas phase, specifically which bonds are broken and where the charge(s) resides in the products. For many peptides, cleavage at the amide bonds dominate, producing a series of ions that are designated b and y. For other peptides, enhanced cleavage occurs at just one or two amino acid residues. Surface-induced dissociation, along with gas-phase collision-induced dissociation performed under a variety of conditions, has been used to refine the general 'mobile proton' model and to determine how and why enhanced cleavages occur at aspartic acid residues and protonated histidine residues. Enhanced cleavage at acidic residues occurs when the charge is unavailable to the peptide backbone or the acidic side-chain. The acidic H of the side-chain then serves to initiate cleavage at the amide bond immediately C-terminal to Asp (or Glu), producing an anhydride. In contrast, enhanced cleavage occurs at His when the His side-chain is protonated, turning His into a weak acid that can initiate backbone cleavage by transferring a proton to the backbone. This allows the nucleophilic nitrogen of the His side-chain to attack and form a cyclic structure that is different from the 'typical' backbone cleavage structures.

Original languageEnglish (US)
Pages (from-to)1399-1406
Number of pages8
JournalJournal of Mass Spectrometry
Issue number12
StatePublished - 2000
Externally publishedYes


  • Collision-induced dissociation
  • Enhanced cleavage
  • Mobile proton
  • Peptide dissociation
  • Surface-induced dissociation

ASJC Scopus subject areas

  • Spectroscopy


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