3K16

Crystal Structure of BRCA1 BRCT D1840T in complex with a minimal recognition tetrapeptide with a free carboxy C-terminus

3K16 の概要

• エントリーDOI: 10.2210/pdb3k16/pdb
• 関連するPDBエントリー: 3K05 3K0H 3K0K 3K14
• 分子名称: Breast cancer type 1 susceptibility protein, phospho peptide, NICKEL (II) ION, ... (5 entities in total)
• 機能のキーワード: brca1, brct domain, dna damage response, phospho peptide interactions, abraxas, isomerase, alternative initiation, cell cycle, disease mutation, dna damage, dna repair, dna-binding, fatty acid biosynthesis, ligase, lipid synthesis, metal-binding, nucleus, phosphoprotein, tumor suppressor, ubl conjugation pathway, zinc-finger
• 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: 2
• 化学式量合計: 25273.06

構造登録者

Campbell, S.J.,Edwards, R.A.,Glover, J.N. (登録日: 2009-09-25, 公開日: 2010-03-02, 最終更新日: 2021-10-13)

主引用文献

Campbell, S.J.,Edwards, R.A.,Glover, J.N.
Comparison of the Structures and Peptide Binding Specificities of the BRCT Domains of MDC1 and BRCA1
Structure, 18:167-176, 2010

PubMed Abstract: The tandem BRCT domains of BRCA1 and MDC1 facilitate protein signaling at DNA damage foci through specific interactions with serine-phosphorylated protein partners. The MDC1 BRCT binds pSer-Gln-Glu-Tyr-COO(-) at the C terminus of the histone variant gammaH2AX via direct recognition of the C-terminal carboxylate, while BRCA1 recognizes pSer-X-X-Phe motifs either at C-terminal or internal sites within target proteins. Using fluorescence polarization binding assays, we show that while both BRCTs prefer a free main chain carboxylate at the +3 position, this preference is much more pronounced in MDC1. Crystal structures of BRCA1 and MDC1 bound to tetrapeptide substrates reveal differences in the environment of conserved arginines (Arg1699 in BRCA1 and Arg1933 in MDC1) that determine the relative affinity for peptides with -COO(-) versus -CO-NH(2) termini. A mutation in MDC1 that induces a more BRCA1-like conformation relaxes the binding specificity, allowing the mutant to bind phosphopeptides lacking a -COO(-) terminus.

PubMed: 20159462
DOI: 10.1016/j.str.2009.12.008

実験手法

X-RAY DIFFRACTION (3 Å)