Structure and ligand recognition of the phosphotyrosine binding domain of Shc

The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of She complexed to a phosphopeptide reveals an alternative means of recognizing tryosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel β-strand with a β-sheet of the protein, interacts with a hydrophobic pocket through the (pY–5) residue, and adopts a β-turn. The PTB domain is structurally similar to pleckstrin homology domains (a β-sandwich capped by an α-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization.