A Combined Experimental and Computational Strategy to Define Protein Interaction Networks for Peptide Recognition Modules
Copyright policy )A Combined Experimental and Computational Strategy to Define Protein Interaction Networks for Peptide Recognition Modules
Peptide recognition modules mediate many protein-protein interactions critical for the assembly of macromolecular complexes. Complete genome sequences have revealed thousands of these domains, requiring improved methods for identifying their physiologically relevant binding partners. We have developed a strategy combining computational prediction of interactions from phage-display ligand consensus sequences with large-scale two-hybrid physical interaction tests. Application to yeast SH3 domains generated a phage-display network containing 394 interactions among 206 proteins and a two-hybrid network containing 233 interactions among 145 proteins. Graph theoretic analysis identified 59 highly likely interactions common to both networks. Las17 (Bee1), a member of the Wiskott-Aldrich Syndrome protein (WASP) family of actin-assembly proteins, showed multiple SH3 interactions, many of which were confirmed in vivo by coimmunoprecipitation.
- University of Mary United States
- University of Washington United States
- Queen's University Canada
- Lunenfeld-Tanenbaum Research Institute Canada
- Mount Sinai Hospital Canada
Protein Structure, Saccharomyces cerevisiae Proteins, Proteome, Settore BIO/18 - GENETICA, Amino Acid Motifs, Molecular Sequence Data, Fungal Protein, src Homology Domain, Saccharomyces cerevisiae, Ligands, Two-Hybrid System Technique, Fungal Proteins, Databases, Genetic, Peptide Library, Consensus Sequence, Databases, Genetic, Cytoskeletal Protein, Amino Acid Sequence, Databases, Protein, Binding Sites, Protein, Binding Site, Computational Biology, Proteins, Protein Structure, Tertiary, Algorithm, Cytoskeletal Proteins, Peptide, Amino Acid Motif, Peptides, Software; Peptide Library; Two-Hybrid System Techniques; Saccharomyces cerevisiae Proteins; Algorithms; Amino Acid Sequence; Wiskott-Aldrich Syndrome Protein; Computational Biology; Protein Binding; Fungal Proteins; src Homology Domains; Saccharomyces cerevisiae; Binding Sites; Amino Acid Motifs; Databases, Protein; Proteome; Molecular Sequence Data; Proteins; Cytoskeletal Proteins; Peptides; Consensus Sequence; Databases, Genetic; Protein Structure, Tertiary; Ligands, Software, Saccharomyces cerevisiae Protein, Wiskott-Aldrich Syndrome Protein, Tertiary, Algorithms, Protein Binding
Protein Structure, Saccharomyces cerevisiae Proteins, Proteome, Settore BIO/18 - GENETICA, Amino Acid Motifs, Molecular Sequence Data, Fungal Protein, src Homology Domain, Saccharomyces cerevisiae, Ligands, Two-Hybrid System Technique, Fungal Proteins, Databases, Genetic, Peptide Library, Consensus Sequence, Databases, Genetic, Cytoskeletal Protein, Amino Acid Sequence, Databases, Protein, Binding Sites, Protein, Binding Site, Computational Biology, Proteins, Protein Structure, Tertiary, Algorithm, Cytoskeletal Proteins, Peptide, Amino Acid Motif, Peptides, Software; Peptide Library; Two-Hybrid System Techniques; Saccharomyces cerevisiae Proteins; Algorithms; Amino Acid Sequence; Wiskott-Aldrich Syndrome Protein; Computational Biology; Protein Binding; Fungal Proteins; src Homology Domains; Saccharomyces cerevisiae; Binding Sites; Amino Acid Motifs; Databases, Protein; Proteome; Molecular Sequence Data; Proteins; Cytoskeletal Proteins; Peptides; Consensus Sequence; Databases, Genetic; Protein Structure, Tertiary; Ligands, Software, Saccharomyces cerevisiae Protein, Wiskott-Aldrich Syndrome Protein, Tertiary, Algorithms, Protein Binding
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