Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition

Mol Cell. 2003 Feb;11(2):471-81. doi: 10.1016/s1097-2765(03)00046-7.


The SH3 domain, which normally recognizes proline-rich sequences, has the potential to bind motifs with an RxxK consensus. To explore this novel specificity, we have determined the solution structure of the Gads T cell adaptor C-terminal SH3 domain in complex with an RSTK-containing peptide, representing its physiological binding site on the SLP-76 docking protein. The SLP-76 peptide engages four distinct binding pockets on the surface of the Gads SH3 domain and upon binding adopts a unique structure characterized by a right-handed 3(10) helix at the RSTK locus, in contrast to the left-handed polyproline type II helix formed by canonical proline-rich SH3 ligands. The structure, and supporting mutagenesis and peptide binding data, reveal a novel mode of ligand recognition by SH3 domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Motifs / genetics
  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Humans
  • In Vitro Techniques
  • Jurkat Cells
  • Ligands
  • Macromolecular Substances
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Phosphoproteins / chemistry*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Proline / chemistry
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Static Electricity
  • src Homology Domains / genetics


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • GRAP2 protein, human
  • Ligands
  • Macromolecular Substances
  • Phosphoproteins
  • Recombinant Proteins
  • SLP-76 signal Transducing adaptor proteins
  • Proline

Associated data

  • PDB/1H3H