Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Struct Mol Biol. 2004 Jun;11(6):519-25. Epub 2004 May 9.

Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1.

Author information

1
Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.

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.

PMID:
15133503
DOI:
10.1038/nsmb776
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center