構造は,CRISPR RNA 誘導監視複合体を遮断するウイルス抑制メカニズムを明らかにする
Saikat Chowdhury1, Joshua Carter2, MaryClare F Rollins2
1Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Cell
|March 25, 2017
まとめ
プロカリオットはウイルスに対する CRISPR 適応免疫を使います ウイルスは抗CRISPR (Acr) タンパク質を進化させ この防御を阻害し 構造レベルでの分子軍拡競争を明らかにしました
科学分野:
- 微生物学
- 分子生物学
- 構造生物学
背景:
- ウイルスと宿主の間の遺伝的対立が 進化の革新を促します
- プロカリオットはCRISPR-Casの適応免疫システムを利用して ウイルス感染から身を守ります
- ウイルスは宿主のCRISPR防御に抵抗する抗CRISPR (Acr) タンパク質を開発しています.
研究 の 目的:
- Pseudomonas aeruginosa のタイプI-F CRISPR-Cas 免疫システムの抗CRISPRタンパク質媒介抑制の構造的基礎を解明する.
- Acrタンパク質がCRISPR媒介のDNAターゲティングを阻害する分子メカニズムを理解する.
主な方法:
- クリオ電子顕微鏡 (cryo-EM) を用いて,AcrF1とAcrF2に結合したCsy複合体の構造を決定した.
- 構造誘導型変異は,観察された相互作用の機能的意義を検証するために使用された.
主要な成果:
- AcrF1とAcrF2のCsy複合体の冷凍-EM構造は3. 4 Åの解像度で決定された.
- 構造は,crRNA誘導監視複合体によるDNA認識に関与する重要な残基に結合することを明らかにする.
- Acr結合は免疫系の機能に不可欠な相互作用を妨害することを変異分析で確認した.
結論:
- この研究は,CRISPR-Cas免疫とウイルスの対抗メカニズムの分子相互作用の構造的なスナップショットを提供しています.
- Acrタンパク質は,Csy複合体のDNA結合と監視能力に直接干渉することによって機能します.
- これらの発見は プロカリオット免疫システムと ウイルスの敵対者の間の 進行中の共進化的軍拡競争を照らしています
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