The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle

J Biol Chem. 2005 Jun 10;280(23):21908-14. doi: 10.1074/jbc.M501258200. Epub 2005 Mar 28.


p130(cas) (Crk-associated substrate) is a docking protein that is involved in assembly of focal adhesions and concomitant cellular signaling. It plays a role in physiological regulation of cell adhesion, migration, survival, and proliferation, as well as in oncogenic transformation. The molecule consists of multiple protein-protein interaction motifs, including a serine-rich region that is positioned between Crk and Src-binding sites. This study reports the first structure of a functional domain of Cas. The solution structure of the serine-rich region has been determined by NMR spectroscopy, demonstrating that this is a stable domain that folds as a four-helix bundle, a protein-interaction motif. The serine-rich region bears strong structural similarity to four-helix bundles found in other adhesion components like focal adhesion kinase, alpha-catenin, or vinculin. Potential sites for phosphorylation and interaction with the 14-3-3 family of cellular regulators are identified in the domain and characterized by site-directed mutagenesis and binding assays. Mapping the degree of amino acid conservation onto the molecular surface reveals a patch of invariant residues near the C terminus of the bundle, which may represent a previously unidentified site for protein interaction.

Publication types

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

MeSH terms

  • 14-3-3 Proteins / chemistry
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Crk-Associated Substrate Protein
  • Cytoskeletal Proteins / chemistry
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation
  • Peptides / chemistry
  • Phosphorylation
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / physiology*
  • Rats
  • Retinoblastoma-Like Protein p130
  • Sequence Homology, Amino Acid
  • Serine / chemistry*
  • Signal Transduction
  • Vinculin / chemistry
  • alpha Catenin


  • 14-3-3 Proteins
  • BCAR1 protein, human
  • Bcar1 protein, mouse
  • Bcar1 protein, rat
  • CTNNA1 protein, human
  • Crk-Associated Substrate Protein
  • Ctnna1 protein, mouse
  • Cytoskeletal Proteins
  • Peptides
  • Proteins
  • Retinoblastoma-Like Protein p130
  • alpha Catenin
  • Vinculin
  • Serine

Associated data

  • PDB/1Z23