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1kzy

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1kzy, resolution 2.50Å ()
Ligands:
Gene: TP53 (Homo sapiens), 53BP1 (Homo sapiens)
Domains: P53, BRCT, BRCT
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

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

Publication Abstract from PubMed

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.

Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure., Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP, Genes Dev. 2002 Mar 1;16(5):583-93. PMID:11877378

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Disease

Known disease associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Choroid plexus papilloma OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Li-Fraumeni-like syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170]

About this Structure

1KZY is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP. Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure. Genes Dev. 2002 Mar 1;16(5):583-93. PMID:11877378 doi:10.1101/gad.959202

Page seeded by OCA on Tue Feb 17 10:41:25 2009

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