Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb

EMBO J. 2000 Apr 3;19(7):1505-15. doi: 10.1093/emboj/19.7.1505.

Abstract

The phosphotyrosine-binding (PTB) domain of the cell fate determinant Numb is involved in the formation of multiple protein complexes in vivo and can bind a diverse array of peptide sequences in vitro. To investigate the structural basis for the promiscuous nature of this protein module, we have determined its solution structure by NMR in a complex with a peptide containing an NMSF sequence derived from the Numb-associated kinase (Nak). The Nak peptide was found to adopt a significantly different structure from that of a GPpY sequence-containing peptide previously determined. In contrast to the helical turn adopted by the GPpY peptide, the Nak peptide forms a beta-turn at the NMSF site followed by another turn near the C-terminus. The Numb PTB domain appears to recognize peptides that differ in both primary and secondary structures by engaging various amounts of the binding surface of the protein. Our results suggest a mechanism through which a single PTB domain might interact with multiple distinct target proteins to control a complex biological process such as asymmetric cell division.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Drosophila Proteins
  • In Vitro Techniques
  • Juvenile Hormones / chemistry*
  • Juvenile Hormones / genetics
  • Juvenile Hormones / metabolism*
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptides / metabolism
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary

Substances

  • Drosophila Proteins
  • Juvenile Hormones
  • Macromolecular Substances
  • Peptides
  • numb protein, Drosophila
  • Phosphotyrosine
  • Nak protein, Drosophila
  • Protein Serine-Threonine Kinases