PDBsum entry 1ayc

Hydrolase(sh2 domain)

PDB id: 1ayc

Contents

Protein chain

100 a.a. *

Ligands

GLY-GLY-PTR-MET-ASP-MET-SER

Waters ×63

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Crystal structures of peptide complexes of the amino-Terminal sh2 domain of the syp tyrosine phosphatase.
• Authors: C.H.Lee, D.Kominos, S.Jacques, B.Margolis, J.Schlessinger, S.E.Shoelson, J.Kuriyan.
• Ref.: Structure, 1994, 2, 423-438. [DOI no: 10.1016/S0969-2126(00)00044-7]
• PubMed id: 7521735

Abstract

BACKGROUND: Src homology 2 (SH2) domains bind to phosphotyrosine residues in a sequence-specific manner, and thereby couple tyrosine phosphorylation to changes in the localization or catalytic activity of signal transducing molecules. Current understanding of SH2 specificity is based on the structures of SH2-peptide complexes of the closely-related Src and Lck tyrosine kinases. The tyrosine phosphatase Syp contains two SH2 domains that are relatively divergent from those of the tyrosine kinases, with distinct target specificities, and is thus well suited for structural studies aimed at extending our understanding of SH2 specificity. RESULTS: Crystal structures of the amino-terminal SH2 domain of Syp in separate complexes with two high-affinity peptides, in complex with a non-specific peptide and in the uncomplexed form have been determined at between 2 A and 3 A resolution. The structure of the SH2 domain and the mode of high-affinity peptide binding is essentially similar to that seen in the Src and Lck structures. However, the binding interface is more extensive in Syp. CONCLUSIONS: Most SH2 targets have hydrophobic residues at the third position following the phosphotyrosine, and the Syp structure confirms that the peptide is anchored to the SH2 surface by this residue and by the phosphotyrosine. In addition, the Syp structure has revealed that sequence specificity can extend across the five residues following the phosphotyrosine, and has shown how the SH2 domain's surface topography can be altered with resulting changes in specificity, while conserving the structure of the central core of the domain.

Figure 4.
Figure 4. Comparison of the Syp and Src SH2 domains. The polypeptide backbones of the Syp and Src SH2 domains are shown as red and white tubes, respectively. The YEEI peptide (Src) is shown in yellow and the IRS1-895 and PDGFR-1009 peptides (Syp) are shown in orange and blue, respectively. The view is approximately perpendicular to the peptide-binding surface. The two structures were first superimposed with the program O [44] and displayed using Insight (Biosym Technologies). Figure 4. Comparison of the Syp and Src SH2 domains. The polypeptide backbones of the Syp and Src SH2 domains are shown as red and white tubes, respectively. The YEEI peptide (Src) is shown in yellow and the IRS1-895 and PDGFR-1009 peptides (Syp) are shown in orange and blue, respectively. The view is approximately perpendicular to the peptide-binding surface. The two structures were first superimposed with the program O [[3]44] and displayed using Insight (Biosym Technologies).

The above figure is reprinted by permission from Cell Press: Structure (1994, 2, 423-438) copyright 1994.

Secondary reference #1

• Title: Binding of a high affinity phosphotyrosyl peptide to the src sh2 domain: crystal structures of the complexed and peptide-Free forms.
• Authors: G.Waksman, S.E.Shoelson, N.Pant, D.Cowburn, J.Kuriyan.
• Ref.: Cell, 1993, 72, 779-790. [DOI no: 10.1016/0092-8674(93)90405-F]
• PubMed id: 7680960

Secondary reference #2

• Title: Structures of sh2 and sh3 domains
• Authors: J.Kuriyan, D.Cowburn.
• Ref.: curr opin struct biol, 1993, 3, 828.

Secondary reference #3

• Title: Crystal structure of the phosphotyrosine recognition domain sh2 of V-Src complexed with tyrosine-Phosphorylated peptides.
• Authors: G.Waksman, D.Kominos, S.C.Robertson, N.Pant, D.Baltimore, R.B.Birge, D.Cowburn, H.Hanafusa, B.J.Mayer, M.Overduin, M.D.Resh, C.B.Rios, L.Silverman, J.Kuriyan.
• Ref.: Nature, 1992, 358, 646-653.
• PubMed id: 1379696