4Y2G

Structure of BRCA1 BRCT domains in complex with Abraxas single phosphorylated peptide

4Y2G の概要

• エントリーDOI: 10.2210/pdb4y2g/pdb
• 分子名称: Breast cancer type 1 susceptibility protein, BRCA1-A complex subunit Abraxas (3 entities in total)
• 機能のキーワード: dna damage response, brct, phosphopeptide, ligase-peptide complex, 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; Nucleus : Q6UWZ7
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26734.58

構造登録者

Wu, Q.,Blundell, T.L. (登録日: 2015-02-09, 公開日: 2016-01-27, 最終更新日: 2024-05-01)

主引用文献

Wu, Q.,Paul, A.,Su, D.,Mehmood, S.,Foo, T.K.,Ochi, T.,Bunting, E.L.,Xia, B.,Robinson, C.V.,Wang, B.,Blundell, T.L.
Structure of BRCA1-BRCT/Abraxas Complex Reveals Phosphorylation-Dependent BRCT Dimerization at DNA Damage Sites.
Mol.Cell, 61:434-448, 2016

PubMed Abstract: BRCA1 accumulation at DNA damage sites is an important step for its function in the DNA damage response and in DNA repair. BRCA1-BRCT domains bind to proteins containing the phosphorylated serine-proline-x-phenylalanine (pSPxF) motif including Abraxas, Bach1/FancJ, and CtIP. In this study, we demonstrate that ionizing radiation (IR)-induces ATM-dependent phosphorylation of serine 404 (S404) next to the pSPxF motif. Crystal structures of BRCT/Abraxas show that phosphorylation of S404 is important for extensive interactions through the N-terminal sequence outside the pSPxF motif and leads to formation of a stable dimer. Mutation of S404 leads to deficiency in BRCA1 accumulation at DNA damage sites and cellular sensitivity to IR. In addition, two germline mutations of BRCA1 are found to disrupt the dimer interface and dimer formation. Thus, we demonstrate a mechanism involving IR-induced phosphorylation and dimerization of the BRCT/Abraxas complex for regulating Abraxas-mediated recruitment of BRCA1 in response to IR.

PubMed: 26778126
DOI: 10.1016/j.molcel.2015.12.017

実験手法

X-RAY DIFFRACTION (2.5 Å)