PYEEI peptide

In addition, it has been determined that introducing single substitutions at the -1-1, -1-2, or -1-3 positions C-terminal to the pTyr of the pYEEI peptide causes only small effects on binding (Bradshaw and Waksman,... 

Binding studies using other Src family member SH2 domains have revealed that these domains have binding properties similar to those of the Src SH2 domain. For instance, several different investigations have determined that Src family SH2 domains bind selectively to the pYEEI peptide, but the level of specificity is modest (1) competition binding assays using both the Lck and Src SH2 domains and radioactive peptides... 

Information about the specificity of SH2 domain binding came initially from the structures of the Src and Lck SH2 domains in complex with tyrosyl phosphopeptides with the sequence Glu, Glu, He (EEI) C-ter-minal to the pTyr (pY) (Eck et al., 1993 Waksman et al., 1993). This pYEEI sequence had previously been identified to be specific for the Src family of SH2 domains, which includes Lck (see Section III). The Src and Lck structures are very similar to one another. Although the peptides employed in both studies contained residues outside the pYEEI motif, the structures indicate that only these four residues contact the SH2 domain. The peptide binds the SH2 domains perpendicular to the central p-sheet in an extended conformation (Fig. 2A). The pTyr makes contacts very similar to those observed for the structure of the Src SH2 domain in complex with low-affinity tyrosyl phosphopeptides (see above). However, in addition, the EEI motif makes specific contact with other residues of the protein. 

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