3PXB

Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: T1700A

3PXB の概要

• エントリーDOI: 10.2210/pdb3pxb/pdb
• 関連するPDBエントリー: 1N5O 1T15 1T2U 1T2V 2ING 3PXA 3PXC 3PXD 3PXE
• 分子名称: Breast cancer type 1 susceptibility protein, SULFATE ION, NICKEL (II) ION, ... (4 entities in total)
• 機能のキーワード: brca1 protein, missense, phosphopeptide recognition, brct tandem repeat, bach1 ctip abraxas, nuclear protein, protein binding
• 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: 1
• 化学式量合計: 24655.96

構造登録者

Coquelle, N.,Green, R.,Glover, J.N.M. (登録日: 2010-12-09, 公開日: 2011-04-20, 最終更新日: 2023-09-13)

主引用文献

Coquelle, N.,Green, R.,Glover, J.N.
Impact of BRCA1 BRCT Domain Missense Substitutions on Phosphopeptide Recognition.
Biochemistry, 50:4579-4589, 2011

PubMed Abstract: The BRCA1 BRCT domain binds pSer-x-x-Phe motifs in partner proteins to regulate the cellular response to DNA damage. Approximately 120 distinct missense variants have been identified in the BRCA1 BRCT through breast cancer screening, and several of these have been linked to an increased cancer risk. Here we probe the structures and peptide-binding activities of variants that affect the BRCA1 BRCT phosphopeptide-binding groove. The results obtained from the G1656D and T1700A variants illustrate the role of Ser1655 in pSer recognition. Mutations at Arg1699 (R1699W and R1699Q) significantly reduce peptide binding through loss of contacts to the main chain of the Phe(+3) residue and, in the case of R1699W, to a destabilization of the BRCT fold. The R1835P and E1836K variants do not dramatically reduce peptide binding, in spite of the fact that these mutations significantly alter the structure of the walls of the Phe(+3) pocket.

PubMed: 21473589
DOI: 10.1021/bi2003795

実験手法

X-RAY DIFFRACTION (2.5 Å)