title: Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin.
abstract: Syntenin has crucial roles in cell adhesion, cell migration and synaptic transmission. Its closely linked postsynaptic density-95, discs large 1, zonula occludens-1 (PDZ) domains typically interact with C-terminal ligands. We profile syntenin PDZ1-2 through proteomic peptide phage display (ProP-PD) using a library that displays C-terminal regions of the human proteome. The protein recognizes a broad range of peptides, with a preference for hydrophobic motifs and has a tendency to recognize cryptic internal ligands. We validate the interaction with nectin-1 through orthogonal assays. The study demonstrates the power of ProP-PD as a complementary approach to uncover interactions of potential biological relevance.
authors.affiliation: Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Aix-Marseille University, Centre National de la Recherche Scientifique UMR7258, Marseille, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Garrido-Urbani
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.|Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Ontario, Canada.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Garg
authors.affiliation: Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Aix-Marseille University, Centre National de la Recherche Scientifique UMR7258, Marseille, France.
authors.forename: Rania
authors.initials: R
authors.lastname: Ghossoub
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.
authors.forename: Roland
authors.initials: R
authors.lastname: Arnold
authors.affiliation: Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Aix-Marseille University, Centre National de la Recherche Scientifique UMR7258, Marseille, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Lembo
authors.affiliation: Department of Chemistry - BMC, Uppsala University, Sweden.
authors.forename: Gustav N
authors.initials: GN
authors.lastname: Sundell
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Kim
authors.affiliation: Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Aix-Marseille University, Centre National de la Recherche Scientifique UMR7258, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Aix-Marseille University, Centre National de la Recherche Scientifique UMR7258, Marseille, France.|Department of Human Genetics, KU Leuven, Belgium.
authors.forename: Pascale
authors.initials: P
authors.lastname: Zimmermann
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.|Banting and Best Department of Medical Research and Department of Molecular Genetics, University of Toronto, Ontario, Canada.
authors.forename: Sachdev S
authors.initials: SS
authors.lastname: Sidhu
authors.affiliation: Department of Chemistry - BMC, Uppsala University, Sweden.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Ivarsson
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D019295:Computational Biology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D055767:Immobilized Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D061986:MCF-7 Cells; D008958:Models, Molecular; D000075983:Nectins; D054731:PDZ Domains; D010446:Peptide Fragments / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D019151:Peptide Library; D040901:Proteomics / Q000379:methods; D011994:Recombinant Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D053676:Syntenins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D015815:Cell Adhesion Molecules; D055767:Immobilized Proteins; D008024:Ligands; C000619010:NECTIN1 protein, human; D000075983:Nectins; D010446:Peptide Fragments; D019151:Peptide Library; D011994:Recombinant Proteins; C109621:SDCBP protein, human; D053676:Syntenins
keywords: PDZ domain; peptide interaction; phage display; protein-protein interaction; short linear motif