Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor.
The BRCT (BRCA1 C-terminus) is an evolutionary conserved protein-protein interacting module found as single, tandem or multiple repeats in a diverse range of proteins known to play roles in the DNA-damage response. The BRCT domains of 53BP1 bind to the tumour suppressor p53. To investigate the nature of this interaction, we have determined the crystal structure of the 53BP1 BRCT tandem repeat in complex with the DNA-binding domain of p53. The structure of the 53BP1-p53 complex shows that the BRCT tandem repeats pack together through a conserved interface that also involves the inter-domain linker. A comparison of the structure of the BRCT region of 53BP1 with the BRCA1 BRCT tandem repeat reveals that the interdomain interface and linker regions are remarkably well conserved. 53BP1 binds to p53 through contacts with the N-terminal BRCT repeat and the inter-BRCT linker. The p53 residues involved in this binding are mutated in cancer and are also important for DNA binding. We propose that BRCT domains bind to cellular target proteins through a conserved structural element termed the 'BRCT recognition motif'.
Structural Medicine Unit, Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK.
Dean J
DJ
Derbyshire
Balaku P
BP
Basu
Louise C
LC
Serpell
Woo S
WS
Joo
Takayasu
T
Date
Kuniyoshi
K
Iwabuchi
Aidan J
AJ
Doherty
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins; D011487:Protein Conformation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000071857:Tumor Suppressor p53-Binding Protein 1
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C498301:TP53BP1 protein, human; D016159:Tumor Suppressor Protein p53; D000071857:Tumor Suppressor p53-Binding Protein 1