1L0B

Crystal Structure of rat Brca1 tandem-BRCT region

1L0B の概要

• エントリーDOI: 10.2210/pdb1l0b/pdb
• 分子名称: BRCA1 (2 entities in total)
• 機能のキーワード: tandem-brct, three-helix bundle, unknown function
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Nucleus (By similarity): O54952
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26104.85

構造登録者

Joo, W.S.,Jeffrey, P.D.,Cantor, S.B.,Finnin, M.S.,Livingston, D.M.,Pavletich, N.P. (登録日: 2002-02-08, 公開日: 2002-03-20, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.3 Å)