Combining peptide recognition specificity and context information for the prediction of the 14-3-3-mediated interactome in S. Cerevisiae and H. Sapiens

Simona Panni, Luisa Montecchi-Palazzi, Lars Kiemer, Andrea Cabibbo, Serena Paoluzi, Elena Santonico, Christiane Landgraf, Rudolf Volkmer-Engert, Angela Bachi, Luisa Castagnoli, Gianni Cesareni

Research output: Contribution to journalArticle

Abstract

Large-scale interaction studies contribute the largest fraction of protein interactions information in databases. However, co-purification of non-specific or indirect ligands, often results in data sets that are affected by a considerable number of false positives. For the fraction of interactions mediated by short linear peptides, we present here a combined experimental and computational strategy for ranking the reliability of the inferred partners. We apply this strategy to the family of 14-3-3 domains. We have first characterized the recognition specificity of this domain family, largely confirming the results of previous analyses, while revealing new features of the preferred sequence context of 14-3-3 phospho-peptide partners. Notably, a proline next to the carboxy side of the phospho-amino acid functions as a potent inhibitor of 14-3-3 binding. The position-specific information about residue preference was encoded in a scoring matrix and two regular expressions. The integration of these three features in a single predictive model outperforms publicly available prediction tools. Next we have combined, by a naïve Bayesian approach, these "peptide features" with "protein features", such as protein co-expression and co-localization. Our approach provides an orthogonal reliability assessment and maps with high confidence the 14-3-3 peptide target on the partner proteins.

Original languageEnglish
Pages (from-to)128-143
Number of pages16
JournalProteomics
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 2011

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Keywords

  • 14-3-3
  • Bioinformatics
  • Domain
  • Interaction networks
  • Phosphopeptide
  • Spot synthesis

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Panni, S., Montecchi-Palazzi, L., Kiemer, L., Cabibbo, A., Paoluzi, S., Santonico, E., Landgraf, C., Volkmer-Engert, R., Bachi, A., Castagnoli, L., & Cesareni, G. (2011). Combining peptide recognition specificity and context information for the prediction of the 14-3-3-mediated interactome in S. Cerevisiae and H. Sapiens. Proteomics, 11(1), 128-143. https://doi.org/10.1002/pmic.201000030