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バクテリアのcGASのような酵素は,多様な核酸信号を合成する
Aaron T Whiteley1,2, James B Eaglesham1,2, Carina C de Oliveira Mann1,2
1Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Nature
|February 22, 2019
まとめ
研究者らは,様々なサイクル型二核酸と三核酸を生成する,新種の細菌酵素である循環型核酸型核酸変異酶 (CD-NTases) を発見した. これらの分子は宿主-病原体相互作用と 微生物コミュニティのダイナミクスに影響します
科学分野:
- 微生物学
- 生物化学
- 構造生物学
背景:
- サイクリック・ディヌクレオチド (CDN) は,ホメオスタシスと毒性に関与する重要な細菌の二次伝達物質である.
- 細菌のCDNは,感染中にパターン認識受容体を通して宿主の免疫反応を誘発することができます.
研究 の 目的:
- バクテリアのシグナル伝達核酸を 体系的に検知する
- CDN合成に関与する新しい酵素を特定する.
- 新しく発見された核チルトランスフェラーゼの構造と機能を特徴づける.
主な方法:
- バクテリアのシグナリング核酸の体系的な生化学的スクリーニング
- タンパク質の発現と浄化
- 酵素構造を決定するX線結晶学.
- 酵素活性と産物形成を分析する生化学的測定法
- ホスト受容体の活性化を評価する細胞測定
主要な成果:
- cGAS/DncV型核チルトランスファーゼ (CD-NTases) の大きなファミリーの発見.
- CD-NTアゼは,ピューリンとピリミジン核酸の両方を用いて多様な周期性二核酸 (CDN) を合成する.
- 構造分析により,核酸選択を担う酵素活性部位が保存されていることが判明した.
- CDNに加えて周期性トリヌクレオチド製品の識別
- これらの周期性分子が 異なる宿主受容体を活性化することを示した.
結論:
- CD-NTasesは,広範な基板特異性を持つ保存された酵素ファミリーを表しています.
- CD-NTアゼによって合成される多様な循環型核酸製品は,宿主-病原体および宿主-微生物群の相互作用を調節することができる.
- これらの発見により 細菌のシグナル伝達分子や 宿主の免疫や生態系への影響について 理解が深まりました
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