プロモーターに結合したTFIIDの構造とヒトの前開始複合体のモデル
Robert K Louder1, Yuan He2,3, José Ramón López-Blanco4
1Biophysics Graduate Group, University of California, Berkeley, California 94720, USA.
Nature
|March 24, 2016
まとめ
一般的な転写因子IID (TFIID) 構造は,DNAを結合し,転写機構を組み立てる方法を明らかにします. これらの発見は,RNAポリメラーゼIIによる遺伝子活性化の基本的メカニズムを明らかにします.
科学分野:
- 分子生物学
- 構造生物学
- 遺伝学
背景:
- 一般転写因子IID (TFIID) は,RNAポリメラーゼII転写の開始に不可欠である.
- TFIIDは,TATA結合タンパク質 (TBP) と13のTBP関連因子 (TAF) を含む大きな複合体です.
- TFIIDは様々なコアプロモーターDNA配列を認識する.
研究 の 目的:
- TFIIAとコアプロモーターDNAに結合するヒトTFIIDの構造を決定する.
- 完全な人間 TAF のない事前開始複合体 (PIC) の組み立てを視覚化する.
- プロモーターの認識と転写の開始における TFIID の役割についての洞察を得ること.
主な方法:
- 単粒子の冷凍電子顕微鏡 (冷凍EM) で,サブナノメートルの解像度.
- 人間のTFIID-TFIIAプロモーターDNA複合体の構造の決定
- ヒトのTAFのないPICの復元は,冷凍EMを使用しています.
主要な成果:
- 構造は,すべてのコアプロモーター要素と接触するTFIIDサブユニットを示し,TAF1とTAF2は下流プロモーターと相互作用します.
- TFIIAはTBP-TATA複合体とTFIIDロブBの間の架け橋として機能する.
- TFIID-DNAとTAFのないPIC構造を比較すると,PIC組立におけるTFIIDの役割が明らかになる.
結論:
- TFIIDは,コアプロモーターDNAを認識し,PICアセンブリを核化する上で中心的な役割を果たします.
- 構造的な洞察は,RNAポリメラーゼIIによる転写開始のメカニズムを明らかにする.
- この発見は遺伝子調節と 潜在的な治療目標の理解のための基盤を提供する.
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