アデノウイルスVA RNAlとタンパク質キナーゼDAIの相互作用:結合と機能の非同等性
K H Mellits1, M Kostura, M B Mathews
1Cold Spring Harbor Laboratory, New York 11724.
Cell
|June 1, 1990
まとめ
アデノウイルスVARNAIは,タンパク質キナーゼDAIの活性化を阻害し,タンパク質合成を維持します. DAIの結合と阻害を媒介する異なるドメインを持つ,その構造は極めて重要です.
科学分野:
- 分子ウイルス学 分子ウイルス学
- タンパク質キナーゼの調節
- RNAの構造と機能の関係
背景:
- アデノウイルスのタンパク質合成は,VA RNAIに依存し,宿主の防御に抵抗します.
- 双鎖RNA (dsRNA) に依存するタンパク質キナーゼ DAI は,タンパク質合成を阻害する.
- VA RNAIはDAIの活性化を阻害することが知られているが,正確なメカニズムは不明である.
研究 の 目的:
- VARNAIの構造と,DAIを結合・抑制する能力との関係を調査する.
- DAIの相互作用と阻害を司るVA RNAIの特定の構造要素を特定する.
主な方法:
- 純化されたDAIと野生型/変異型VARNAを用いたインビトロ結合測定法.
- VA RNAI-DAIの相互作用を確認するためのUVクロスリンク.
- VARNAsの二次構造分析. VARNAsの二次構造分析. VARNAsの二次構造分析. VARNAsの二次構造分析.
- DAI抑制を in vivo で評価するための機能的測定法.
主要な成果:
- VA RNAIは,浄化されたDAIと結合し,この相互作用はUVクロスリンクによって確認できます.
- VA RNAIとDAIの効率的なインビトロ結合は,常にin vivo機能と相関していたわけではない.
- アピカル幹のループ構造は,VA RNAIがDAIと結合するために重要です.
- VA RNAIの中央ドメインは,DAIの活性化を阻害するために重要である.
結論:
- VA RNAIは,DAIと結合し,その活動を抑制するために,異なる構造ドメインを使用します.
- VA RNAIの二重幹は,DAIのdsRNA結合部位と相互作用する可能性が高い.
- VA RNAIは,その中央ドメインを酵素の活性部位の近くに置き,DAIの活性化を阻害する.
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