2LCC

Solution structure of RBBP1 chromobarrel domain

2LCC の概要

• エントリーDOI: 10.2210/pdb2lcc/pdb
• 関連するPDBエントリー: 2LCD
• NMR情報: BMRB: 17606
• 分子名称: AT-rich interactive domain-containing protein 4A (1 entity in total)
• 機能のキーワード: chromobarrel domain, rbbp1, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P29374
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9082.26

構造登録者

Gong, W.,Feng, Y. (登録日: 2011-04-28, 公開日: 2012-02-08, 最終更新日: 2024-05-15)

主引用文献

Gong, W.,Zhou, T.,Mo, J.,Perrett, S.,Wang, J.,Feng, Y.
Structural insight into recognition of methylated histone tails by retinoblastoma-binding protein 1.
J.Biol.Chem., 2012

PubMed Abstract: Retinoblastoma-binding protein 1 (RBBP1), also named AT-rich interaction domain containing 4A (ARID4A), is a tumor and leukemia suppressor involved in epigenetic regulation in leukemia and Prader-Willi/Angelman syndromes. Although the involvement in epigenetic regulation is proposed to involve its chromobarrel and/or Tudor domains because of their potential binding to methylated histone tails, the structures of these domains and their interactions with methylated histone tails are still uncharacterized. In this work, we first found that RBBP1 contains five domains by bioinformatics analysis. Three of the five domains, i.e. chromobarrel, Tudor, and PWWP domains, are Royal Family domains, which potentially bind to methylated histone tails. We further purified these domains and characterized their interaction with methylated histone tails by NMR titration experiments. Among the three Royal Family domains, only the chromobarrel domain could recognize trimethylated H4K20 (with an affinity of ∼3 mm), as well as recognizing trimethylated H3K9, H3K27, and H3K36 (with lower affinities). The affinity could be further enhanced up to 15-fold by the presence of DNA. The structure of the chromobarrel domain of RBBP1 determined by NMR spectroscopy has an aromatic cage. Mutagenesis analysis identified four aromatic residues of the cage as the key residues for methylated lysine recognition. Our studies indicate that the chromobarrel domain of RBBP1 is responsible for recognizing methylated histone tails in chromatin remodeling and epigenetic regulation, which presents a significant advance in our understanding of the mechanism and relationship between RBBP1-related gene suppression and epigenetic regulation.

PubMed: 22247551
DOI: 10.1074/jbc.M111.299149

実験手法

SOLUTION NMR