8OFF

Structure of BARD1 ARD-BRCTs in complex with H2AKc15ub nucleosomes (Map1)

これはPDB形式変換不可エントリーです。

8OFF の概要

• エントリーDOI: 10.2210/pdb8off/pdb
• 関連するPDBエントリー: 8OFF
• EMDBエントリー: 16859 17928
• 分子名称: DNA (142-MER), Histone H3.1, Histone H2B type 1-C/E/F/G/I, ... (7 entities in total)
• 機能のキーワード: brca1-bard1, chromatin recognition, nucleosomes, ubiquitin, dna binding protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 506205.59

構造登録者

Foglizzo, M.,Burdett, H.,Wilson, M.D.,Zeqiraj, E. (登録日: 2023-03-15, 公開日: 2023-10-11, 最終更新日: 2023-11-22)

主引用文献

Burdett, H.,Foglizzo, M.,Musgrove, L.J.,Kumar, D.,Clifford, G.,Campbell, L.J.,Heath, G.R.,Zeqiraj, E.,Wilson, M.D.
BRCA1-BARD1 combines multiple chromatin recognition modules to bridge nascent nucleosomes.
Nucleic Acids Res., 51:11080-11103, 2023

PubMed Abstract: Chromatin association of the BRCA1-BARD1 heterodimer is critical to promote homologous recombination repair of DNA double-strand breaks (DSBs) in S/G2. How the BRCA1-BARD1 complex interacts with chromatin that contains both damage induced histone H2A ubiquitin and inhibitory H4K20 methylation is not fully understood. We characterised BRCA1-BARD1 binding and enzymatic activity to an array of mono- and di-nucleosome substrates using biochemical, structural and single molecule imaging approaches. We found that the BRCA1-BARD1 complex preferentially interacts and modifies di-nucleosomes over mono-nucleosomes, allowing integration of H2A Lys-15 ubiquitylation signals with other chromatin modifications and features. Using high speed- atomic force microscopy (HS-AFM) to monitor how the BRCA1-BARD1 complex recognises chromatin in real time, we saw a highly dynamic complex that bridges two nucleosomes and associates with the DNA linker region. Bridging is aided by multivalent cross-nucleosome interactions that enhance BRCA1-BARD1 E3 ubiquitin ligase catalytic activity. Multivalent interactions across nucleosomes explain how BRCA1-BARD1 can recognise chromatin that retains partial di-methylation at H4 Lys-20 (H4K20me2), a parental histone mark that blocks BRCA1-BARD1 interaction with nucleosomes, to promote its enzymatic and DNA repair activities.

PubMed: 37823591
DOI: 10.1093/nar/gkad793

実験手法

ELECTRON MICROSCOPY (3.4 Å)