purin 抑制剤によるコアプレッサー媒介の特定のDNA結合のメカニズム
M A Schumacher1, K Y Choi, F Lu
1Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
Cell
|October 6, 1995
まとめ
小分子エフェクターは,DNA結合タンパク質の親和性を調節する. コアプレッサーを除去すると,ピューリンレプレッサーが発生します.
科学分野:
- 構造生物学 構造生物学とは
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- 小分子エフェクターは,通常,プロカリオットとユーカリオットにおけるDNA結合タンパク質の親和性を調節する.
- 遠端タンパク質ドメインによるDNA結合のエフェクター誘発アロステリック調節のメカニズムは,構造的に理解されていないままです.
研究 の 目的:
- purin 抑制器におけるエフェクター調節DNA結合の構造的メカニズムを解明する.
- コアプレッサー結合が,このプレッサーファミリーのDNA相互作用にどのように影響するかを理解するために.
主な方法:
- 初期研究で,コアプレッサーとpurFオペレーターに結合したピューリン抑制器の結晶構造を決定しました.
- 2.2 Åの解像度でピューリン抑制器のコアプレッサーフリーコアプレッサー結合ドメインの結晶構造を決定しました.
主要な成果:
- 構造分析により,コアプレッサー結合ポケットの構造の変化が,結合されていない状態で顕著であったことが明らかになった.
- 各サブユニットは,コアプレッサーを外したときに最大23度まで開くように回転しました.
- この回転は,小型の溝結合ヒンジヘリクスを解き放ち,抑制剤-DNA解離につながります.
結論:
- purin 圧縮器は,コア圧縮器の結合と放出時に実質的な形状の変化を経験します.
- DNA結合のアロステリック調節は,大規模なドメインの移動によって媒介されます.
- これは,抑制器におけるエフェクター調節DNA結合を理解するための構造的基礎を提供します.
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