dsRNAウイルスの内部にある分割されたゲノムとRNAポリメラーゼ複合体のインシット構造
Xing Zhang1, Ke Ding2,3, Xuekui Yu2
1California Nanosystems Institute, Los Angeles, CA 90095, USA.
Nature
|October 28, 2015
まとめ
研究者らは,細胞プラズマ多面症ウイルス (CPV) の転写酵素複合体 (TEC) の構造を明らかにした. ウイルスのRNA合成に不可欠なこの複合体は,環境のシグナルで転写を活性化するために形状を変化させます.
科学分野:
- 構造的ウイルス学
- 分子生物学
- RNAウイルスの転写
背景:
- ロータウイルスと細胞膜多重症ウイルス (CPV) を含むReoviridaeファミリーのウイルスは,分割された二重鎖RNA (dsRNA) ゲノムを持っています.
- これらのウイルスは,カプシド内の転写酵素複合体 (TEC) を使用して内部でメッセンジャーRNA (mRNA) を合成します.
研究 の 目的:
- 静止状態のCPV (q-CPV) 内のdsRNAゲノムの組織を決定する.
- 静止状態 (q-CPV) と転写状態 (t-CPV) の TEC の in situ 原子構造を解明する.
主な方法:
- 電子を数える冷凍電子顕微鏡
- アシンメトリックな再構築技術
- ウイルスの構成要素の構造分析
主要な成果:
- 10個の分割されたdsRNAは10個のTECで非対称的に組織され,各dsRNAセグメントはTECに直接結合している.
- TECは2つの相互作用するサブユニット:RNA依存RNAポリメラーゼ (RdRP) とNTPase VP4で構成されています.
- q-CPVからt-CPVへの変換時にRdRPブレスレットドメインの形状の変化は,RNAテンプレートエントリーチャネルを作成し,ポリメラーゼ活性サイトを活性化します.
- カプシドシェルタンパク質 (CSP) のサブユニットは,VP4とRdRPと相互作用し,外部のキューセンシングとTECの活性化を結びつける.
結論:
- この研究では,dSRNAゲノムとTECがCPV内で正確に組織されていることが明らかになりました.
- 構造的な洞察は,RdRPの構造的変化を含むTEC活性化のメカニズムを示しています.
- 発見は,カプシドタンパク質による外部環境感知とウイルスのRNA転写の開始との関係を確立した.
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