Molecular roots of degenerate specificity in syntenin's PDZ2 domain: reassessment of the PDZ recognition paradigm

Structure. 2003 Jul;11(7):845-53. doi: 10.1016/s0969-2126(03)00125-4.

Abstract

Crystal structures of the PDZ2 domain of the scaffolding protein syntenin, both unbound and in complexes with peptides derived from C termini of IL5 receptor (alpha chain) and syndecan, reveal the molecular roots of syntenin's degenerate specificity. Three distinct binding sites (S(0), S(-1), and S(-2)), with affinities for hydrophobic side chains, function in a combinatorial way: S(-1) and S(-2) act together to bind syndecan, while S(0) and S(-1) are involved in the binding of IL5Ralpha. Neither mode of interaction is consistent with the prior classification scheme, which defined the IL5Ralpha interaction as class I (-S/T-X-phi) and the syndecan interaction as class II (-phi-X-phi). These results, in conjunction with other emerging structural data on PDZ domains, call for a revision of their classification and of the existing model of their mechanism.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Proteoglycans / metabolism
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-5
  • Serine / metabolism
  • Syndecans
  • Syntenins

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Proteoglycans
  • Receptors, Interleukin
  • Receptors, Interleukin-5
  • SDCBP protein, human
  • Syndecans
  • Syntenins
  • Serine

Associated data

  • PDB/1NTE
  • PDB/1OBX
  • PDB/1OBY