Structure and ligand recognition of the phosphotyrosine binding domain of Shc

Nature. 1995 Dec 7;378(6557):584-92. doi: 10.1038/378584a0.

Abstract

The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of Shc complexed to a phosphopeptide reveals an alternative means of recognizing tyrosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the protein, interacts with a hydrophobic pocket through the (pY-5) residue, and adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology domains (a beta-sandwich capped by an alpha-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Binding Sites
  • Blood Proteins / chemistry
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Phospholipids / metabolism
  • Phosphopeptides / chemistry
  • Phosphopeptides / metabolism
  • Phosphoproteins*
  • Phosphotyrosine / metabolism*
  • Protein Conformation
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Proteins / metabolism
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, trkA
  • Receptors, Nerve Growth Factor / chemistry
  • Receptors, Nerve Growth Factor / metabolism
  • Shc Signaling Adaptor Proteins
  • Signal Transduction
  • src Homology Domains

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Blood Proteins
  • Ligands
  • Peptide Fragments
  • Phospholipids
  • Phosphopeptides
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, Nerve Growth Factor
  • Shc Signaling Adaptor Proteins
  • platelet protein P47
  • Phosphotyrosine
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA