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PTB Domain
Class:Phospho-Tyr binding

No Image The PTB domains of Shc and IRS-1 contain two orthogonal b-sheets and connecting loops, and have very similar folds despite their low sequence similarity. Both have a C-terminal amphipathic a-helix capping one end of the b-sandwich. The N-terminal residues of the peptide ligand form an additional anti-parallel b-strand to the second b-sheet. The figure shows the PTB domain of Shc complexed to a HIIENPQpYFSDA peptide.

Structure Reference:
Zhou, MM. et al. (1995) Nature. 378(6557): 584-92. PDB: 1SHC.

Domain binding and function:
Phosphotyrosine binding (PTB) domains are 100-150 residue modules that commonly bind Asn-Pro-X-Tyr motifs. The PTB domains of the docking proteins Shc and IRS-1 require ligand phosphorylation on the tyrosine residue (NPXpY) for binding. More N-terminal sequences are also required for high affinity binding and conferring specificity. The peptide binds as a b-strand to an anti-parallel b-sheet, while the NPXpY motif makes a turn, positioning 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.
Examples of Proteins: 
PTB domain protein
Binding partner
Shc docking protein TrkA Nerve Growth Factor Receptor: Ile-Ile-Asn-Pro-Gln-pTyr
IRS-1 docking protein Insulin receptor: Leu-Tyr-Ala-Ser-Ser-Asn-Pro-Glu-pTyr
X11 neuronal protein b-amyloid precursor protein: Tyr-Glu-Asn-Pro-Thr-Tyr

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