CREBのトランザクティベーションドメインに結合したCBPのKIXドメインのソリューション構造:アクティベーター:コアクティベーターの相互作用のモデル
I Radhakrishnan1, G C Pérez-Alvarado, D Parker
1Department of Molecular Biology, and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Cell
|December 31, 1997
まとめ
CREBタンパク質は,CREBタンパク質と
科学分野:
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
- バイオケミストリー バイオケミストリー
背景:
- CREB (cAMP応答要素結合タンパク質) は,遺伝子発現を調節する転写因子である.
- CREBは,CBP (CREB結合タンパク質) のようなコアクティベータとの相互作用を通じて転写を活性化します.
- CREBのリン酸化は,CBPとの相互作用において極めて重要です.
研究 の 目的:
- リン酸化CREBとCBPのKIXドメインの相互作用の構造的基礎を決定する.
- CREBのpKID (リン酸化キナーゼ誘導ドメイン) がKIXに結合する方法を明らかにする.
主な方法:
- CREB pKID-KIX複合体の溶液構造の決定.
- タンパク質とタンパク質の相互作用と構造変化の分析.
主要な成果:
- CREB pKIDは,KIXと結合するとコイルからヘリックスへの移行を経て,2つのアルファヘリクスを形成します.
- pKID alphaBヘリクスは,KIX (ヘリクスの alpha1 と alpha3) にある水嫌性の溝に結合する.
- pKIDのフォスフォセリンとKIXのTyr-658の間に重要な水素結合が形成されます.
結論:
- この研究は,CREB-CBPの相互作用の詳細な構造的メカニズムを明らかにしています.
- これは,他のトランザクションのドメイン-ターゲット相互作用を理解するためのモデルを提供します.
- CREBにおけるリン酸化に依存する形状の変化は,コアクティベーター結合に極めて重要です.
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