Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: crystal structures of the complexed and peptide-free forms

Cell. 1993 Mar 12;72(5):779-90. doi: 10.1016/0092-8674(93)90405-f.

Abstract

The crystal structure of the Src SH2 domain complexed with a high affinity 11-residue phosphopeptide has been determined at 2.7 A resolution by X-ray diffraction. The peptide binds in an extended conformation and makes primary interactions with the SH2 domain at six central residues: PQ(pY)EEI. The phosphotyrosine and the isoleucine are tightly bound by two well-defined pockets on the protein surface, resulting in a complex that resembles a two-pronged plug engaging a two-holed socket. The glutamate residues are in solvent-exposed environments in the vicinity of basic side chains of the SH2 domain, and the two N-terminal residues cap the phosphotyrosine-binding site. The crystal structure of Src SH2 in the absence of peptide has been determined at 2.5 A resolution, and comparison with the structure of the high affinity complex reveals only localized and relatively small changes.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Glutamates / metabolism
  • Glutamic Acid
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphopeptides / metabolism*
  • Protein Conformation
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Sequence Alignment
  • Tyrosine / metabolism
  • X-Ray Diffraction

Substances

  • Glutamates
  • Phosphopeptides
  • Glutamic Acid
  • Tyrosine
  • Proto-Oncogene Proteins pp60(c-src)