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

doi:10.1016/0092-8674(93)90405-F

Cell

Volume 72, Issue 5, 12 March 1993, Pages 779-790

https://doi.org/10.1016/0092-8674(93)90405-F Get rights and content

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.

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Citation Excerpt :
As expected, the N- to C-terminal orientation of the bound phosphopeptide is consistent with other SH2 domain structures (18) and is dictated by placing pTyr1087 into the deep electrostatic pocket and Pro1090 into the shallow cleft, recapitulating canonical electrostatic and van der Waals interactions (Fig. 1D). The residues of p120RasGAP C-SH2 that contact the phosphopeptide are generally similar to previously studied SH2–phosphopeptide interactions (16, 18, 48) (Fig. 1, E and F). Curiously, however, we observed that the FLVR motif arginine residue, Arg377, is oriented differently to other SH2 domains in both the apo and peptide-bound crystal forms.
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Cell

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

Abstract

J. Biol. Chem.,

Cell

Cell

J. Biol. Chem.,

Trends Cell Biol.,

Cell

Cell

J. Mol. Biol.,

Phosphatidylinositol 3′-kinase is activated by association with IRS-1 during insulin stimulation

EMBO J.

Structure of an SH2 domain of the p85α subunit of phosphatidylinositol-3-OH kinase

Nature

Extension of molecular replacement: a new search strategy based on Patterson correlation refinement

Acta Crystallogr.,

Identification of a protein that binds to the SH3 region of abl and is similar to Bcr and GAP-rho

Science

Inhibition of SH2 domain/phosphoprotein association by a nonhydrolyzable phosphonopeptide

Biochemistry

A phosphatidylinositol 3-kinase binds to platelet-derived growth factor receptors through a specific receptor sequence containing phosphotyrosine

Mol. Cell. Biol.,

The binding of SH2 domains to tyrosine phosphorylated peptides exhibits high affinity binding yet rapid dissociation and exchange

Mol. Cell. Biol.,

Calculating the electrostatic potential of molecules in solution: method and error assessment

J. Comp. Chem.,

Model bias in macromolecular structures

Acta Crystallogr.,

Improved methods for building protein models in electron density maps and the location of errors in these models

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Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo

EMBO J.

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