サイクルヌクレオチド活性化CRISPRプロテアゼによる抗ウイルスシグナル伝達
Christophe Rouillon1,2, Niels Schneberger3, Haotian Chi4
1Institute of Structural Biology, University of Bonn, Bonn, Germany. back2crispr@gmail.com.
Nature
|November 24, 2022
まとめ
CRISPRに関連したLonプロテアゼ (CalpL) は,CalpTを割ってCalpSを放出し,外来核酸検出をプロカリオットの転写調節と関連付けます. これはCRISPRシステムと 抗菌体シグナル伝達との関連を示しています
科学分野:
- 微生物学
- 分子生物学
- 構造生物学
背景:
- CRISPR防御システムは,DNA標的型Cas9とRNA標的型IIIを含むが,プロカリオートでは一般的である.
- タイプIIIのCRISPRシステムは,異種RNAを検出すると,周期性オリゴアデニラート合成によって抗ウイルス反応を開始する.
- CRISPRに関連したLonプロテアゼ (CalpL) を含むタイプIIIシステムに関連するタンパク質は,周期性オリゴアデニラートを結合すると予測されています.
研究 の 目的:
- CRISPR関連ロンプロテアゼ (CalpL) の構造と機能を明らかにする.
- CalpLがCRISPR関連複合体の他のタンパク質と相互作用するメカニズムを理解する.
- CRISPR媒介による外来核酸認識と下流の規制イベントの間のリンクを確立する.
主な方法:
- CalpLタンパク質の構造分析
- 三重複合体内の CalpL の機能を決定する生化学的測定.
- 相互作用するタンパク質 (CalpTとCalpS) を特定するためのオペロン分析.
主要な成果:
- CalpLは,CalpTとCalpSと安定した三重複合体を形成する.
- 活性化されたCalpLは,MazFのホモログであるCalpTをオリゴメリゼスし,分割する.
- CalpTの割れは,細胞外機能シグマ因子 CalpSを放出する.
- CalpLは,サイクルテトラアデニlate (cA4) を結合する SAVED ドメインを有する.
結論:
- この研究では,外来核酸のCRISPR検出と転写制御の間の直接的な関連が示されています.
- この発見は,SAVEDドメインのCRISPRエフェクタと,サイクルオリゴヌクレオチドベースの抗菌シグナル伝達システムの関連性を明らかにした.
- CalpLの機能は,プロカリオットの抗ウイルス防御と遺伝子調節のための新しいメカニズムを強調しています.
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