Detection of peptides, proteins, and drugs that selectively interact with protein targets

• Published in: Genome research 2002-11, Vol.12 (11), p.1785-1791
• Main Authors: Serebriiskii, Ilya G, Mitina, Olga, Pugacheva, Elena N, Benevolenskaya, Elizaveta, Kotova, Elena, Toby, Garabet G, Khazak, Vladimir, Kaelin, William G, Chernoff, Jonathan, Golemis, Erica A
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Motifs - genetics; Amino Acid Sequence - genetics; Animals; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae - chemistry; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae - genetics; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae - metabolism; Cloning, Molecular; Databases, Protein; Genome; Genome, Fungal; Genome, Human; Humans; Methods; Molecular Sequence Data; Peptides - genetics; Peptides - metabolism; Pharmaceutical Preparations - metabolism; Phosphoproteins - chemistry; Phosphoproteins - genetics; Phosphoproteins - metabolism; Pilot Projects; Protein Interaction Mapping - methods; Proteins - chemistry; Proteins - genetics; Proteins - metabolism; Proteome - chemistry; Proteome - genetics; Proteome - metabolism; Retinoblastoma Protein - chemistry; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism
• ISSN: 1088-9051; 1054-9803; 1549-5469
• DOI: 10.1101/gr.450702

Genome sequencing has been completed for multiple organisms, and pilot proteomic analyses reported for yeast and higher eukaryotes. This work has emphasized the facts that proteins are frequently engaged in multiple interactions, and that governance of protein interaction specificity is a primary means of regulating biological systems. In particular, the ability to deconvolute complex protein interaction networks to identify which interactions govern specific signaling pathways requires the generation of biological tools that allow the distinction of critical from noncritical interactions. We report the application of an enhanced Dual Bait two-hybrid system to allow detection and manipulation of highly specific protein-protein interactions. We summarize the use of this system to detect proteins and peptides that target well-defined specific motifs in larger protein structures, to facilitate rapid identification of specific interactors from a pool of putative interacting proteins obtained in a library screen, and to score specific drug-mediated disruption of protein-protein interaction.