title: Combining peptide recognition specificity and context information for the prediction of the 14-3-3-mediated interactome in S. cerevisiae and H. sapiens.
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.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy. simona.panni@uniroma2.it
authors.forename: Simona
authors.initials: S
authors.lastname: Panni
authors.forename: Luisa
authors.initials: L
authors.lastname: Montecchi-Palazzi
authors.forename: Lars
authors.initials: L
authors.lastname: Kiemer
authors.forename: Andrea
authors.initials: A
authors.lastname: Cabibbo
authors.forename: Serena
authors.initials: S
authors.lastname: Paoluzi
authors.forename: Elena
authors.initials: E
authors.lastname: Santonico
authors.forename: Christiane
authors.initials: C
authors.lastname: Landgraf
authors.forename: Rudolf
authors.initials: R
authors.lastname: Volkmer-Engert
authors.forename: Angela
authors.initials: A
authors.lastname: Bachi
authors.forename: Luisa
authors.initials: L
authors.lastname: Castagnoli
authors.forename: Gianni
authors.initials: G
authors.lastname: Cesareni
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D010748:Phosphopeptides / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D010455:Peptides; D010748:Phosphopeptides