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Systematic Identification of Single Amino Acid Variants in Glioma Stem-Cell-Derived Chromosome 19 Proteins

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Author

  • Cheryl Lichti
  • Ekaterina Mostovenko
  • Paul Wadsworth
  • Gillian Lynch
  • Montgomery Pettitt
  • Erik Sulman
  • Qiunghu Wang
  • Frederick Lang
  • Melinda Rezeli
  • György Marko-Varga
  • Ákos Végvári
  • Carol Nilsson
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Summary, in English

Novel proteoforms with single amino acid polymorphism represent proteins that often have altered biological functions but are less explored in the human proteome. We have developed an approach, searching high quality shotgun proteomic data against an extended protein database, to identify expressed mutant proteoforms in glioma stem cell (GSC) lines. The systematic search of MS/MS spectra has recognized 13 chromosome 19 proteins in GSCs with altered amino acid sequences using PEAKS 7.0 as the search engine. The results were further verified by manual spectral examination, validating 14 proteoforms. One of the novel findings, a mutant form of branched-chain aminoacyl transferase 2 (T186R), was verified at the transcript level and by SRM in several glioma stem cell lines. The structure of this proteoform examined by molecular modeling to estimate structural changes of mutation that could lead to functional modifications potentially linked to glioma. Based on our initial findings, we believe that our approach presented could contribute to construct a more complete map of the human functional proteome.

Publishing year

2015

Language

English

Pages

778-786

Publication/Series

Journal of Proteome Research

Volume

14

Issue

2

Document type

Journal article

Publisher

The American Chemical Society (ACS)

Topic

  • Medical Engineering

Keywords

  • Chromosome-centric Human Proteome Project
  • Chromosome 19
  • Mass spectrometry
  • Non-synonymous single nucleotide polymorphism
  • amino acid polymorphism
  • Glioma stem cells
  • Cancer proteomics
  • bioinformatics
  • SRM assay
  • BCAT2 T186R

Status

Published

ISBN/ISSN/Other

  • ISSN: 1535-3893