Summary
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.
Method X-RAY DIFFRACTION
Structure factors resolution 2.5 rfactor 0.216 rfree 0.256
DPI 0.86 theoretical min: 0.36
Related PDB Entries 1L0B
Citations

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