• DOI:10.1074/jbc.C200571200
• Corpus ID: 12053468

Novel Mode of Ligand Recognition by the Erbin PDZ Domain*

@article{Birrane2003NovelMO,
  title={Novel Mode of Ligand Recognition by the Erbin PDZ Domain*},
  author={Gabriel Birrane and Ju Young Chung and John A. A. Ladias},
  journal={The Journal of Biological Chemistry},
  year={2003},
  volume={278},
  pages={1399 - 1402}
}

• G. Birrane, J. Chung, J. Ladias
• Published 17 January 2003
• Chemistry, Biology
• The Journal of Biological Chemistry

Erbin contains a class I PDZ domain that binds to the C-terminal region of the receptor tyrosine kinase ErbB2, a class II ligand. The crystal structure of the human Erbin PDZ bound to the peptide EYLGLDVPV corresponding to the C-terminal residues 1247–1255 of human ErbB2 has been determined at 1.25-Å resolution. The Erbin PDZ deviates from the canonical PDZ fold in that it contains a single α-helix. The isopropyl group of valine at position −2 of the ErbB2 peptide interacts with the Erbin Val1351and displaces the peptide backbone away from the α-helix, elucidating the molecular basis of class II ligand recognition by a class I PDZ domain. Strikingly, the phenolic ring of tyrosine −7 enters into a pocket formed by the extended β2-β3 loop of the Erbin PDZ. Phosphorylation of tyrosine −7 abolishes this interaction but does not affect the binding of the four C-terminal peptidic residues to PDZ, as revealed by the crystal structure of the Erbin PDZ complexed with a phosphotyrosine-containing ErbB2 peptide. Since phosphorylation of tyrosine −7 plays a critical role in ErbB2 function, the selective binding and sequestration of this residue in its unphosphorylated state by the Erbin PDZ provides a novel mechanism for regulation of the ErbB2-mediated signaling and oncogenicity.