A Combined Experimental and Computational Strategy to Define Protein Interaction Networks for Peptide Recognition Modules

Amy H.Y. Tong; Becky Drees; Giuliano Nardelli; Gary D. Bader; Barbara Brannetti; Luisa Castagnoli; Marie Evangelista; Silvia Ferracuti; Bryce Nelson; Serena Paoluzi; Michele Quondam; Adriana Zucconi; Christopher W.V. Hogue; Stanley Fields; Charles Boone; Gianni Cesareni

doi:10.1126/science.1064987

Abstract

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.

Keywords

Protein–protein interactionComputational biologyPhage displayTwo-hybrid screeningBiologyImmunoprecipitationPeptideInteraction networkComputer scienceYeastGeneticsGeneBiochemistry

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Publication Info

Year: 2002
Type: article
Volume: 295
Issue: 5553
Pages: 321-324
Citations: 711
Access: Closed

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APA Style

                            
                                
                                    Amy H.Y. Tong, 
                                
                                    Becky Drees, 
                                
                                    Giuliano Nardelli
                                
                                et al.
                            
                            (2002). 
                            A Combined Experimental and Computational Strategy to Define Protein Interaction Networks for Peptide Recognition Modules. 
                            Science
                            , 295
                            (5553)
                            , 321-324.
                            https://doi.org/10.1126/science.1064987
                        

Identifiers

DOI: 10.1126/science.1064987