Li, S.C., Zwahlen, C., Vincent, S.J., McGlade, C.J., Kay, L.E., Pawson, T., Forman-Kay, J.D. (1998). Structure of a Numb PTB domain-peptide complex suggests a basis for diverse binding specificity.  Nat. Struct. Biol. 5(12): 1075--1083.

FBrf0105874

Research paper

The phosphotyrosine-binding (PTB) domain of Numb, a protein involved in asymmetric cell division, has recently been shown to bind to the adapter protein Lnx through an LDNPAY sequence, to the Numb-associated kinase (Nak) through a sequence that does not contain an NPXY motif and to GP(p)Y-containing peptides obtained from library screening. We show here that these diverse peptide sequences bind with comparable affinities to the Numb PTB domain at a common binding site on the surface of the protein. The NMR structure of the Numb PTB domain in complex with a GPpY-containing peptide reveals a novel mechanism of binding with the peptide in a helical turn that does not hydrogen bond to the PTB domain beta-sheet. These results suggest that PTB domains can potentially have multiple modes of peptide recognition and provide a structural basis from which the multiple functions of the Numb PTB domain during asymmetric cell division could arise.