ヒストンアセチルトランスフェラーゼブロモドメインの構造とリガンド
C Dhalluin1, J E Carlson, L Zeng
1Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Nature
|June 12, 1999
まとめ
研究者らは,P/CAFのブロモドメイン構造を発見し,これは重要な転写共同活性化剤である. この研究では,ブロモドメインがアセチル化されたリシンに特異的に結合し,遺伝子の調節におけるヒストンアセチルトランスフェラーゼ (HAT) 活性と結合することを明らかにした.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- ヒストンのアセチル化は,クロマチンの改造と遺伝子活性化に不可欠です.
- ブロモドメインはヒストンアセチルトランスファーゼ (HAT) 関連転写共同活性化剤の一般的なモジュールである.
- ブロモドメインの構造と結合相手は以前は知られていなかった.
研究 の 目的:
- P/CAFブロモドメインの3次元構造を決定する.
- ブロモドメインの結合相互作用を調査する.
- ブロモドメインとHATの活動との機能的関連を理解する.
主な方法:
- P/CAFブロモドメインの溶液構造の決定.
- サイト・ディレクテッド・ミュータジェネシス研究.
- タンパク質-アセチル化されたリジン相互作用の分析.
主要な成果:
- P/CAFブロモドメインは,珍しい左利き4ヘリックスバンドル構造を採用しています.
- ブロモドメインは,アセチル化ライシン残基を特異的に認識し,結合する.
- この相互作用は,HATsによるアセチル-CoA結合に類似しています.
結論:
- ブロモドメインは,アセチル化リジンを特異的に結合する最初の特定されたタンパク質モジュールです.
- ブロモドメインのアセチル・ライシン結合は,共同活性化剤のHAT活性と機能的に関連しています.
- この発見は,遺伝子転写調節のメカニズムについての洞察を提供します.
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