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CSL-Notch-Mastermind三重複合体の結晶構造は,DNAに結合している

Jeffrey J Wilson¹, Rhett A Kovall

¹Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

|March 15, 2006

まとめ

この研究は,キーノッチ信号複合体の構造を明らかにしています. この発見は,CSLタンパク質が発達中の遺伝子転写を抑制から活性化へと切り替える仕組みを説明しています.

科学分野:

分子生物学は分子生物学である.
発達生物学発達生物学について
構造生物学構造生物学とは

背景:

ノッチ・シグナリングは,細胞のコミュニケーション,胚のパターニング,そして発達に不可欠です.
CSL (CBF1/Su(H) /Lag-1) は,コレギュレータと相互作用することによって,ノッチ標的遺伝子を調節する転写因子です.
トランスクリプションの活性化には,CSLからコアプレッサーをNotch細胞内領域 (NotchIC) によって移動させ,Mastermindコアクティベーターを勧誘する.

研究の目的:

CSL,NotchIC,MastermindがDNAに結合した三元複合体の構造を決定する.
Notch-mediatedの転写活性化に伴う分子メカニズムを解明する.

主な方法:

X線結晶学を用いて,三元複合体の3.1 Å構造を決定した.
複合体内のタンパク質-タンパク質相互作用の分析.

主要な成果:

NotchのRAMドメインは,予想通り,CSLベータトリフォイルドメインと相互作用する.
CSLのC端末ドメインは,Notch ankyrin repeatsとMastermindとのインターフェースにおいて,重要かつ予期せぬ役割を果たしています.
三元複合体の形成は,CSLにおける重要な形状の変化を誘導する.

結論:

この構造は,CSLが抑制体から活性化体へとどのように移行するかの分子基礎を提供する.
転写活性化のための相互作用を媒介するCSLC端末ドメインの重要な役割を強調しています.
Notchシグナル伝達経路による遺伝子発現の調節に関する洞察を提供します.

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