Sc. Li et al., Structure of a Numb PTB domain-peptide complex suggests a basis for diverse binding specificity, NAT ST BIOL, 5(12), 1998, pp. 1075-1083
The phosphotyrosine-binding (PTB) domain of Numb, a protein involved in asy
mmetric cell division, has recently been shown to bind to the adapter prote
in Lnx through an LDNPAY sequence, to the Numb-associated kinase (Nak) thro
ugh a sequence that does not contain an NPXY motif and to CP(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 nov
el mechanism of binding with the peptide in a helical turn that does not hy
drogen bond to the PTB domain P-sheet. These results suggest that PTB domai
ns 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.