Global investigation of protein–protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences

Abstract

Protein–protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of ∼99.95% and executes 16 000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29 589 high confidence interactions of ∼2 × 107 possible pairs. Of these, 14 438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations.

Bck2 is a phase-independent activator of cell cycle-regulated genes in yeast

“…79,81,82 Intriguingly, a computational prediction for Bck2-interacting proteins produced seven hits, namely, Kss1, Fus3, Smi1, Slt2, YKL161C, Ino4 and Pho85. 83 In view of these data, it is tempting to speculate that Bck2 might be targeted to gene promoters via its interaction with a diverse set of recruited kinases. Once at these promoters, Bck2 might contribute to the full expression of its gene targets.…”

Short Co-occurring Polypeptide Regions Can Predict Global Protein Interaction Maps

“…For more details, please see17. To measure sequence similarity, the PAM120 substitution matrix is used.…”

Evolution of protein-protein interaction networks in yeast

“…PIPE has been used to identify novel protein interactions, to discover new protein complexes, to predict novel protein functions [32–36], and to produce proteome-wide predicted interaction networks for S . cerevisiae [34], Schizosaccharomyces pombe [33], Caenorhabditis elegans [35] and Homo sapiens [36], among others.…”