Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1.
The C-terminal BRCT region of BRCA1 is essential for its DNA repair, transcriptional regulation and tumor suppressor functions. Here we determine the crystal structure of the BRCT domain of human BRCA1 at 2.5 A resolution. The domain contains two BRCT repeats that adopt similar structures and are packed together in a head-to-tail arrangement. Cancer-causing missense mutations occur at the interface between the two repeats and destabilize the structure. The manner by which the two BRCT repeats interact in BRCA1 may represent a general mode of interaction between homologous domains within proteins that interact to regulate the cellular response to DNA damage. The structure provides a basis to predict the structural consequences of uncharacterized BRCA1 mutations.
Williams
R S
RS
Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Green
R
R
Glover
J N
JN
D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000737:chemistry* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D018360:Crystallography, X-Ray; D016147:Genes, Tumor Suppressor; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009154:Mutation; D010449:Peptide Mapping; D011487:Protein Conformation; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid
D019313:BRCA1 Protein