Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/7521735http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/7521735http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/7521735http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(00)00044-7"xsd:string
http://purl.uniprot.org/citations/7521735http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(00)00044-7"xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Kuriyan J."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Kuriyan J."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Lee C.-H."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Lee C.-H."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Margolis B."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Margolis B."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Schlessinger J."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Schlessinger J."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Shoelson S.E."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Shoelson S.E."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Kominos D."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Kominos D."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Jacques S."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/author"Jacques S."xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/date"1994"xsd:gYear
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/date"1994"xsd:gYear
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/pages"423-438"xsd:string
http://purl.uniprot.org/citations/7521735http://purl.uniprot.org/core/pages"423-438"xsd:string
▶