"Affinity-proteomics": direct protein identification from biological material using mass spectrometric epitope mapping

Anal Bioanal Chem. 2004 Feb;378(4):1102-11. doi: 10.1007/s00216-003-2159-8. Epub 2003 Aug 30.

Abstract

We describe here a new approach for the identification of affinity-bound proteins by proteolytic generation and mass spectrometric analysis of their antibody bound epitope peptides (epitope excision). The cardiac muscle protein troponin T was chosen as a protein antigen because of its diagnostic importance in myocardial infarct, and its previously characterised epitope structure. Two monoclonal antibodies (IgG1-1B10 and IgG1-11.7) raised against intact human troponin T were found to be completely cross reactive with bovine heart troponin T. A combination of immuno-affinity isolation, partial proteolytic degradation (epitope excision), mass spectrometric peptide mapping, and database analysis was used for the direct identification of Tn T from bovine heart cell lysate. Selective binding of the protein was achieved by addition of bovine heart cell lysate to the Sepharose-immobilised monoclonal antibodies, followed by removal of supernatant material containing unbound protein. While still bound to the affinity matrix the protein was partially degraded thereby generating a set of affinity-bound, overlapping peptide fragments comprising the epitope. Following dissociation from the antibody the epitope peptides were analysed by matrix assisted laser desorption-ionisation (MALDI) and electrospray-ionisation (ESI) mass spectrometry. The peptide masses identified by mass spectrometry were used to perform an automated database search, combined with a search for a common "epitope motif". This procedure resulted in the unequivocal identification of the protein from biological material with only a minimum number of peptide masses, and requiring only limited mass-determination accuracy. The dramatic increase of selectivity for identification of the protein by combining the antigen-antibody specificity with the redundancy of peptide sequences renders this "affinity-proteomics" approach a powerful tool for mass spectrometric identification of proteins from biological material.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Binding Sites
  • Epitope Mapping / methods*
  • Epitopes / analysis*
  • Epitopes / chemistry
  • Epitopes / immunology
  • Heart
  • In Vitro Techniques
  • Molecular Sequence Data
  • Peptides / analysis
  • Peptides / chemistry
  • Peptides / immunology
  • Proteins / analysis*
  • Proteins / chemistry*
  • Proteins / immunology
  • Proteomics / methods*
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Troponin T / analysis
  • Troponin T / chemistry
  • Troponin T / immunology

Substances

  • Antibodies
  • Epitopes
  • Peptides
  • Proteins
  • Troponin T