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

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)205-219
Number of pages15
JournalJournal of Biomolecular NMR
Volume27
Issue number3
DOIs
Publication statusPublished - 1 Nov 2003
Externally publishedYes

Keywords

  • Breast cancer
  • Growth factor receptor bound
  • NMR
  • Receptor tyrosine kinase
  • Src homology

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