1KZY

Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53

Summary for 1KZY

• Entry DOI: 10.2210/pdb1kzy/pdb
• Descriptor: CELLULAR TUMOR ANTIGEN P53, TUMOR SUPPRESSOR P53-BINDING PROTEIN 1, ZINC ION, ... (4 entities in total)
• Functional Keywords: tandem-brct and linker complexed with non-brct protein, three-helix bundle, parallel beta sheet, dna binding protein, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637; Nucleus: Q12888
• Total number of polymer chains: 4
• Total formula weight: 102558.84

Authors

Joo, W.S.,Jeffrey, P.D.,Cantor, S.B.,Finnin, M.S.,Livingston, D.M.,Pavletich, N.P. (deposition date: 2002-02-08, release date: 2002-03-20, Last modification date: 2024-10-16)

Primary citation

Joo, W.S.,Jeffrey, P.D.,Cantor, S.B.,Finnin, M.S.,Livingston, D.M.,Pavletich, N.P.
Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure.
Genes Dev., 16:583-593, 2002

PubMed Abstract: 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.

PubMed: 11877378
DOI: 10.1101/gad.959202

Experimental method

X-RAY DIFFRACTION (2.5 Å)