1T2V

Structural basis of phospho-peptide recognition by the BRCT domain of BRCA1, structure with phosphopeptide

1T2V の概要

• エントリーDOI: 10.2210/pdb1t2v/pdb
• 関連するPDBエントリー: 1JNX 1N5O 1T2U
• 分子名称: Breast cancer type 1 susceptibility protein, BRCTide-7PS (2 entities in total)
• 機能のキーワード: brct, brca1, breast cancer, cell signaling, missense mutation, phosphopeptide, antitumor 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
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 131921.36

構造登録者

Williams, R.S.,Lee, M.S.,Hau, D.D.,Glover, J.N.M. (登録日: 2004-04-22, 公開日: 2004-05-11, 最終更新日: 2024-10-30)

主引用文献

Williams, R.S.,Lee, M.S.,Hau, D.D.,Glover, J.N.M.
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1
Nat.Struct.Mol.Biol., 11:519-525, 2004

PubMed Abstract: The BRCT repeats in BRCA1 are essential for its tumor suppressor activity and interact with phosphorylated protein targets containing the sequence pSer-X-X-Phe, where X indicates any residue. The structure of the tandem BRCA1 BRCT repeats bound to an optimized phosphopeptide reveals that the N-terminal repeat harbors a conserved BRCT phosphoserine-binding pocket, while the interface between the repeats forms a hydrophobic groove that recognizes the phenylalanine. Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition. The diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.

PubMed: 15133503
DOI: 10.1038/nsmb776

実験手法

X-RAY DIFFRACTION (3.3 Å)