Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin

FEBS Lett. 2016 Jan;590(1):3-12. doi: 10.1002/1873-3468.12037. Epub 2016 Jan 8.

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.

Keywords: PDZ domain; peptide interaction; phage display; protein-protein interaction; short linear motif.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • COS Cells
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Chlorocebus aethiops
  • Computational Biology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Immobilized Proteins / chemistry
  • Immobilized Proteins / genetics
  • Immobilized Proteins / metabolism
  • Kinetics
  • Ligands
  • MCF-7 Cells
  • Models, Molecular*
  • Nectins
  • PDZ Domains
  • Peptide Fragments / chemistry
  • Peptide Fragments / classification
  • Peptide Fragments / metabolism
  • Peptide Library
  • Proteomics / methods
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / classification
  • Recombinant Proteins / metabolism
  • Syntenins / chemistry
  • Syntenins / genetics
  • Syntenins / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Cell Adhesion Molecules
  • Immobilized Proteins
  • Ligands
  • NECTIN1 protein, human
  • Nectins
  • Peptide Fragments
  • Peptide Library
  • Recombinant Proteins
  • SDCBP protein, human
  • Syntenins