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 develop...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2002-01, Vol.295 (5553), p.321-324
Main Authors: Amy Hin Yan Tong, Drees, Becky, Nardelli, Giuliano, Bader, Gary D., Brannetti, Barbara, Castagnoli, Luisa, Evangelista, Marie, Ferracuti, Silvia, Nelson, Bryce, Paoluzi, Serena, Quondam, Michele, Zucconi, Adriana, Christopher W. V. Hogue, Fields, Stanley, Boone, Charles, Cesareni, Gianni
Format: Article
Language:English
Subjects:
Actins
Algorithms
Amino Acid Motifs
Amino Acid Sequence
Amino acids
Bacteriophages
Binding Sites
Biological and medical sciences
Computational Biology
Consensus Sequence
Cytoskeletal Proteins
Databases, Genetic
Databases, Protein
Datasets
Fundamental and applied biological sciences. Psychology
Fungal Proteins - chemistry
Fungal Proteins - metabolism
Genomes
Libraries
Ligands
Literary Devices
Molecular and cellular biology
Molecular Sequence Data
Molecules
Peptide Library
Peptides
Peptides - chemistry
Peptides - metabolism
Protein Binding
Protein Structure, Tertiary
Proteins
Proteins - chemistry
Proteins - metabolism
Proteome
Proteomes
Saccharomyces cerevisiae - chemistry
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Social Networks
Software
src Homology Domains
Synthetic materials
Two-Hybrid System Techniques
Wiskott-Aldrich Syndrome Protein
Yeasts
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Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1064987