High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides

Nat Struct Biol. 1994 Aug;1(8):546-51. doi: 10.1038/nsb0894-546.

Abstract

Src-homology 3 (SH3) domains bind to proline-rich motifs in target proteins. We have determined high-resolution crystal structures of the complexes between the SH3 domains of Abl and Fyn tyrosine kinases, and two ten-residue proline-rich peptides derived from the SH3-binding proteins 3BP-1 and 3BP-2. The X-ray data show that the basic mode of binding of both proline-rich peptides is the same. Peptides are bound over their entire length and interact with three major sites on the SH3 molecules by both hydrogen-bonding and van der Waals contacts. Residues 4-10 of the peptide adopt the conformation of a left-handed polyproline helix type II. Binding of the proline at position 2 requires a kink at the non-proline position 3.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Chemical Phenomena
  • Chemistry, Physical
  • Crystallography, X-Ray
  • Humans
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Models, Molecular*
  • Molecular Sequence Data
  • Peptides / metabolism*
  • Proline / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary*
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-abl / chemistry*
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Proto-Oncogene Proteins c-fyn
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Substrate Specificity

Substances

  • Peptides
  • Proto-Oncogene Proteins
  • Proline
  • FYN protein, human
  • Proto-Oncogene Proteins c-abl
  • Proto-Oncogene Proteins c-fyn