1T15

Crystal Structure of the Brca1 BRCT Domains in Complex with the Phosphorylated Interacting Region from Bach1 Helicase

1T15 の概要

• エントリーDOI: 10.2210/pdb1t15/pdb
• 分子名称: Breast cancer type 1 susceptibility protein, BRCA1 interacting protein C-terminal helicase 1 (3 entities in total)
• 機能のキーワード: protein-peptide complex, antitumor protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus. Isoform 3: Cytoplasm. Isoform 5: Cytoplasm: P38398
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25493.16

構造登録者

Clapperton, J.A.,Manke, I.A.,Lowery, D.M.,Ho, T.,Haire, L.F.,Yaffe, M.B.,Smerdon, S.J. (登録日: 2004-04-15, 公開日: 2004-05-11, 最終更新日: 2024-10-30)

主引用文献

Clapperton, J.A.,Manke, I.A.,Lowery, D.M.,Ho, T.,Haire, L.F.,Yaffe, M.B.,Smerdon, S.J.
Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer
Nat.Struct.Mol.Biol., 11:512-518, 2004

PubMed Abstract: Germline mutations in the BRCA1 tumor suppressor gene often result in a significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. We report the X-ray crystal structure at a resolution of 1.85 A of the BRCA1 tandem BRCT domains in complex with a phosphorylated peptide representing the minimal interacting region of the DEAH-box helicase BACH1. The structure reveals the determinants of this novel class of BRCA1 binding events. We show that a subset of disease-linked mutations act through specific disruption of phospho-dependent BRCA1 interactions rather than through gross structural perturbation of the tandem BRCT domains.

PubMed: 15133502
DOI: 10.1038/nsmb775

実験手法

X-RAY DIFFRACTION (1.85 Å)