PTB Protein Domain

Phosphotyrosine binding (PTB) domains are 100–150 residue modules that commonly bind Asn-Pro-X-Tyr motifs. The PTB domains of docking proteins Shc and IRS-1 require ligand phosphorylation on the tyrosine residue (NPXpY) for binding. Additional N-terminal sequences are also required for high affinity binding and conferring specificity. The peptide binds as a β-strand to an anti-parallel β-sheet, while the NPXpY motif makes a turn to position the pY for recognition by basic residues. The PTB domains of proteins such as X11, Dab, Fe65 and Numb apparently recognize NPXY or related peptide motifs, but are not dependent on ligand phosphorylation. In addition, the Numb PTB domain can bind an unrelated peptide that forms a helical turn.