バクテリアのNLRに関連するタンパク質は,ファグに対して保護します

Emily M Kibby¹, Amy N Conte¹, A Maxwell Burroughs²

¹Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA.

Cell

|May 9, 2023

まとめ

バクテリアは動物性NLRと同型のNACHTタンパク質を持ち,ファグの感染を防ぎます. これらの古代のタンパク質は人間を含む生命体全体で共有された先天的な免疫メカニズムを示しています

科学分野:

微生物学
免疫学
分子生物学

背景:

細菌は様々な免疫経路を使って病原菌の感染と戦う.
いくつかの細菌の免疫遺伝子は,真核の先天性免疫システムの構成要素に同質性を示し,水平遺伝子の移転を示唆している.
ヌクレオチド結合ドメインとルシン含有リピート (NLR) タンパク質は,動物の先天的免疫,特に炎症体の活性化に中心的です.

研究の目的:

バクテリアのNACHTモジュールを含むタンパク質の存在と機能を調査する.
バクテリアのNACHTタンパク質がファグの感染に対する免疫を提供するかどうかを判断する.
バクテリアと真核細胞のNACHTタンパク質の進化的関係と共有されたシグナルメカニズムを探求する.

主な方法:

バクテリアのゲノムに含まれる NACHT タンパク質を特定するためのバイオ情報分析.
バクテリアのNACHTタンパク質のDNAとRNAファージに対する免疫機能を評価するファージチャレンジアッセイ.
細菌とヒトのNLRタンパク質のドメイン構造の比較分析.
バクテリアのNACHTタンパク質とヒトの変異したNLRを用いて信号伝達経路を調査する機能分析.

主要な成果:

NACHTモジュールを含むタンパク質は,バクテリアで広く存在します.
バクテリアのNACHTタンパク質は,DNAとRNAファグの両方に免疫を与えます.
これらのタンパク質は,真核細胞のNLRに類似した保存されたモジュール構造 (センサ,NACHT,エフェクタ) を表している.
人間のNLRにおける構成性炎症ゾームの活性化を引き起こす変異は,細菌のNACHTタンパク質を活性化させ,保存されたシグナル伝達を示す.

結論:

NACHTタンパク質は細菌や真核生物に保存されている生まれながらの免疫の古代の媒介者です
バクテリアのNACHTタンパク質の発見は,真核細胞のNLRと炎症体の進化的起源についての洞察を提供します.
この研究はバクテリアから人間に至る生命の樹全体における生まれつきの免疫の分子基盤を強調しています

キーワード:

ナイト NLR についてスタンドバクテリオファージ炎症ゾーム生まれつきの免疫ファージ防御

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