抗ウイルス型IIIのCRISPR信号はATPとSAMの結合による

Haotian Chi¹, Ville Hoikkala^1,2, Sabine Grüschow¹

¹Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK.

|October 18, 2023

まとめ

Bacteroides fragilisのタイプIII-BのCRISPRシステムは,抗ウイルス防御のためにS-アデノシルメチオニン-AMP (SAM-AMP) を使用するが,循環性オリゴアデニラートではない. この新しい2番目のメッセンジャーは膜タンパク質を標的にしプロカリオトの免疫に対する新たな洞察を提供しています

科学分野:

分子生物学
微生物学
免疫学

背景:

プロカリオットのCRISPRシステムは移動性遺伝子要素に対する適応免疫を提供します.
タイプIIIのCRISPRシステムは,CRISPRRNAとCas10を使用して,外来核酸を検出し,除去する.
防御のためにCORAやフォスフォディエステラーゼのような非特徴化されたタンパク質が含まれるタイプIIIのシステムもある.

研究の目的:

バクテロイド・フレジリスのCORA関連型III-B (Cmr) CRISPRシステムの抗ウイルス防御機構を調査する.
B. fragilis Cmrシステムの免疫反応に関与するシグナル伝達分子とエフェクターを解明する.
このCRISPRシステムによって生成された新しい2番目のメッセンジャーの特徴です

主な方法:

エシェリキア・コライにおけるB. fragilis Cmr CRISPRシステムの発現
CRISPRシステムの活性化時に生成されるシグナル分子の分析
生成された分子とCORAエフェクターの相互作用の生化学的特徴.

主要な成果:

B. フレジリスのCmrシステムは,E. コリの移動性遺伝要素に対する免疫を与えます.
循環性オリゴアデニラートではなく,S-アデノシルメチオニン-AMP (SAM-AMP) をS-アデノシルメチオニン (SAM) に結合して生成する.
SAM- AMPはCORAエフェクタと結合し,膜の完全性を破壊し,細胞の休眠状態または死につながる可能性があります.

結論:

SAM-AMPは,プロカリオット抗ウイルスシグナル伝達に関与する新種のセカンドメッセンジャーです.
B. フレジリスのCmrシステムは,タイプIIIのCRISPR免疫の独特なメカニズムを表しています.
特定の酵素によるSAM- AMPの分解は,免疫反応のための潜在的な"オフスイッチ"を提供します.

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