1T29

Crystal structure of the BRCA1 BRCT repeats bound to a phosphorylated BACH1 peptide

1T29 の概要

• エントリーDOI: 10.2210/pdb1t29/pdb
• 分子名称: Breast cancer type 1 susceptibility protein, BACH1 phosphorylated peptide (3 entities in total)
• 機能のキーワード: brca1, brct repeats, bach1, phosphopeptide recognition, breast cancer, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus. Isoform 3: Cytoplasm. Isoform 5: Cytoplasm: P38398; Nucleus: Q9BX63
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26209.00

構造登録者

Shiozaki, E.N.,Gu, L.,Yan, N.,Shi, Y. (登録日: 2004-04-20, 公開日: 2004-05-11, 最終更新日: 2024-11-20)

主引用文献

Shiozaki, E.N.,Gu, L.,Yan, N.,Shi, Y.
Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling.
Mol.Cell, 14:405-412, 2004

PubMed Abstract: The recognition of the phosphorylated BACH1 helicase by the BRCA1 C-terminal (BRCT) repeats is important to the tumor suppressor function of BRCA1. Here we report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution. The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT repeats. This surface cleft is highly conserved in BRCA1 across species, suggesting an evolutionarily conserved function of phosphopeptide recognition. Importantly, conserved amino acids critical for BACH1 binding are frequently targeted for missense mutations in breast cancer. These mutations greatly diminish the ability of BRCA1 to interact with the phosphorylated BACH1 peptide. Additional structural analysis revealed significant implications for understanding the function of the BRCT family of proteins in DNA damage and repair signaling.

PubMed: 15125843
DOI: 10.1016/S1097-2765(04)00238-2

実験手法

X-RAY DIFFRACTION (2.3 Å)