PDB 1KZY deposited: 2002-02-08 modified: 2009-02-24
Title Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53
Authors Cantor, S.B., Finnin, M.S., Jeffrey, P.D., Joo, W.S., Livingston, D.M., Pavletich, N.P.
Structure factors resolution 2.5 rfactor 0.216 rfree 0.256
DPI 0.86 theoretical min: 0.36
Related PDB Entries 1L0B

Brca1 C-terminal (BRCT) domains are a common protein-protein interaction motif in proteins involved in the DNA damage response and DNA repair. The DNA-damage response protein 53BP1 has two BRCT domains that bind to the DNA-binding domain of p53. The 53BP1 tandem-BRCT region is homologous to the tandem-BRCT region of Brca1, which is involved in double-strand break repair and homologous recombination and which binds BACH1, a member of the DEAH helicase family. Here we report the structures of a human 53BP1-p53 complex and of the rat Brca1 BRCT repeats. The 53BP1-p53 structure shows that the two BRCT repeats are arranged tandemly and pack extensively through an interface that also involves the inter-repeat linker. The first BRCT repeat and the linker together bind p53 on a region that overlaps with the DNA-binding surface of p53 and involves p53 residues that are mutated in cancer and are important for DNA binding. Comparison with the structure of the tandem-BRCT region of Brca1 shows a remarkable conservation of the repeat arrangement and of the inter-BRCT repeat interface. Analysis of human BRCA1 tumor-derived mutations and conservation identifies a potential protein-binding site that we show through mutagenesis is involved in BACH1 binding. The BACH1-binding region of Brca1 consists of a unique insertion in the first BRCT repeat and the inter-repeat linker and is analogous to the region of 53BP1 that binds p53.

Genes Dev. 2002 Mar; 16(5):583-593 doi:10.1101/gad.959202

Cross References
Database source Identifier Description
PubMed 11877378 GEDEEP
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1KZY/1 1KZY 1 tetramer 0 4 2 6106