1T2V

Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1

(2004) Nat Struct Mol Biol 11: 519-525

• PubMed: 15133503 Search on PubMed
• DOI: https://doi.org/10.1038/nsmb776
• Primary Citation of Related Structures:  
  1T2U, 1T2V


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.