Systematic identification of single amino acid variants in glioma stem-cell-derived chromosome 19 proteins

Cheryl F. Lichti, Ekaterina Mostovenko, Paul A. Wadsworth, Gillian C. Lynch, B. Montgomery Pettitt, Erik P. Sulman, Qianghu Wang, Frederick F. Lang, Melinda Rezeli, György Marko-Varga, Ákos Végvári, Carol L. Nilsson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Novel proteoforms with single amino acid variations 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 using PEAKS 7.0 as the search engine has recognized 17 chromosome 19 proteins in GSCs with altered amino acid sequences. The results were further verified by manual spectral examination, validating 19 proteoforms. One of the novel findings, a mutant form of branched-chain aminotransferase 2 (p.Thr186Arg), was verified at the transcript level and by targeted proteomics in several glioma stem cell lines. The structure of this proteoform was examined by molecular modeling in order to estimate conformational changes due to mutation that might 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.

Original languageEnglish (US)
Pages (from-to)778-786
Number of pages9
JournalJournal of Proteome Research
Volume14
Issue number2
DOIs
StatePublished - Feb 6 2015

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Keywords

  • BCAT2 p.Thr186Arg
  • Chromosome-Centric Human Proteome Project
  • SRM assay
  • bioinformatics
  • cancer proteomics
  • chromosome 19
  • glioma stem cells
  • mass spectrometry
  • missense single nucleotide variants
  • single amino acid variants

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Lichti, C. F., Mostovenko, E., Wadsworth, P. A., Lynch, G. C., Pettitt, B. M., Sulman, E. P., Wang, Q., Lang, F. F., Rezeli, M., Marko-Varga, G., Végvári, Á., & Nilsson, C. L. (2015). Systematic identification of single amino acid variants in glioma stem-cell-derived chromosome 19 proteins. Journal of Proteome Research, 14(2), 778-786. https://doi.org/10.1021/pr500810g