厳格なコントロールのリボソーム依存活性化
Alan Brown1, Israel S Fernández1, Yuliya Gordiyenko1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nature
|June 10, 2016
まとめ
バクテリアの生存は ストレスを感じ取ることに依存しています 研究者らは構造的にRelA酵素が停滞したリボソームに結合して 厳格な反応を誘発し 重要な生存メカニズムとなり 新しい抗菌薬の標的となる ことを明らかにした.
科学分野:
- 微生物学
- 分子生物学
- 構造生物学
背景:
- 細菌はストレス反応を通して 環境の変化に適応します
- 栄養不足によって引き起こされる 厳格な制御は 細菌の代謝と遺伝子発現を 生存のために再プログラムします
- RelAによって合成されるアラームホルモン (p) ppGppは,この反応の核心です.
研究 の 目的:
- RelAがバクテリアのリボソームに結合する構造的メカニズムを解明する.
- RelAがアミノアシレートされたtRNAと未充電をどのように区別するかを理解する.
- 抗菌薬の開発においてRelAをターゲットにするための構造的基盤を提供すること.
主な方法:
- 細菌のリボソームに結合するRelAの構造を決定するために,冷凍電子顕微鏡 (cryo-EM) を使用した.
- 構造的発見を検証するために生化学的測定が暗示された.
主要な成果:
- 凍結EM構造は,他の転化因子とは異なる,停滞したリボソームのRelAのユニークな結合部位を明らかにします.
- RelAのマルチドメインアーキテクチャは,歪んだAサイトtRNAと相互作用する.
- RelAのTGSドメインは,アミノアシレイテッドtRNAの結合をステリックに防止し, (p) ppGpp合成を促進する.
結論:
- この構造は,停滞したリボソームによるRelA活性化と,充電されたtRNAに対する差別化を説明する.
- このメカニズムは ストレス下での細菌の生存に不可欠な 厳格な反応を誘発します
- RelAは病原菌に対する新しい治療法の開発に有望なターゲットです.
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