Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain

Crystal structures of the complexed and peptide-free forms

Gabriel Waksman, Steven E. Shoelson, Nalin Pant, David Cowburn, John Kuriyan

Research output: Contribution to journalArticle

625 Citations (Scopus)

Abstract

The crystal structure of the Src SH2 domain complexed with a high affinity 11-residue phosphopeptide has been determined at 2.7 Å 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 Å resolution, and comparison with the structure of the high affinity complex reveals only localized and relatively small changes.

Original languageEnglish (US)
Pages (from-to)779-790
Number of pages12
JournalCell
Volume72
Issue number5
DOIs
StatePublished - Mar 12 1993
Externally publishedYes

Fingerprint

Src peptide
Phosphotyrosine
src Homology Domains
Crystal structure
Phosphopeptides
Peptides
Isoleucine
Conformations
Glutamic Acid
Membrane Proteins
Binding Sites
X-Ray Diffraction
X ray diffraction

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain : Crystal structures of the complexed and peptide-free forms. / Waksman, Gabriel; Shoelson, Steven E.; Pant, Nalin; Cowburn, David; Kuriyan, John.

In: Cell, Vol. 72, No. 5, 12.03.1993, p. 779-790.

Research output: Contribution to journalArticle

Waksman, Gabriel ; Shoelson, Steven E. ; Pant, Nalin ; Cowburn, David ; Kuriyan, John. / Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain : Crystal structures of the complexed and peptide-free forms. In: Cell. 1993 ; Vol. 72, No. 5. pp. 779-790.
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