2nmb

Publication Abstract from PubMed

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.

Structure of a Numb PTB domain-peptide complex suggests a basis for diverse binding specificity.,Li SC, Zwahlen C, Vincent SJ, McGlade CJ, Kay LE, Pawson T, Forman-Kay JD Nat Struct Biol. 1998 Dec;5(12):1075-83. PMID:9846878^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.