Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1

Nat Struct Mol Biol. 2004 Jun;11(6):519-25. doi: 10.1038/nsmb776. Epub 2004 May 9.


The BRCT repeats in BRCA1 are essential for its tumor suppressor activity and interact with phosphorylated protein targets containing the sequence pSer-X-X-Phe, where X indicates any residue. The structure of the tandem BRCA1 BRCT repeats bound to an optimized phosphopeptide reveals that the N-terminal repeat harbors a conserved BRCT phosphoserine-binding pocket, while the interface between the repeats forms a hydrophobic groove that recognizes the phenylalanine. Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition. The diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • BRCA1 Protein / chemistry
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • Binding Sites
  • Breast Neoplasms / etiology
  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Female
  • Humans
  • Molecular Structure
  • Mutation
  • Phosphopeptides / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Transfection


  • BRCA1 Protein
  • Phosphopeptides

Associated data

  • PDB/1T2U
  • PDB/1T2V