Journal of Biomolecular NMR

, Volume 27, Issue 3, pp 205–219 | Cite as

Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2

  • Monika Ivancic
  • Roger J. Daly
  • Barbara A. Lyons

Abstract

The solution structure of the hGrb7-SH2 domain in complex with a ten amino acid phosphorylated peptide ligand representative of the erbB2 receptor tyrosine kinase (pY1139) is presented as determined by nuclear magnetic resonance methods. The hGrb7-SH2 domain structure reveals the Src homology 2 domain topology consisting of a central β-sheet capped at each end by an α-helix. The presence of a four residue insertion in the region between β-strand E and the EF loop and resulting influences on the SH2 domain/peptide complex structure are discussed. The binding conformation of the erbB2 peptide is in a β-turn similar to that found in phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our knowledge this is only the second example of an SH2 domain binding its naturally occurring ligands in a turn, instead of extended, conformation. Close contacts between residues responsible for binding specificity in hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect of mutation of these residues on the hGrb7-SH2 domain structure is discussed.

breast cancer growth factor receptor bound NMR receptor tyrosine kinase Src Homology 

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Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Monika Ivancic
    • 1
  • Roger J. Daly
    • 2
  • Barbara A. Lyons
    • 2
  1. 1.Department of BiochemistryUniversity of Vermont College of MedicineBurlingtonU.S.A
  2. 2.Cancer Research ProgramGarvan Institute of Medical Research, St. Vincent's HospitalSidneyAustralia

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