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シングルファグタンパク質は,TIRおよびcGASのような酵素からの信号を隔離する

Dong Li¹, Yu Xiao^2,3, Iana Fedorova⁴

¹State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.

|October 31, 2024

まとめ

バクテリオファージはTad1とTad2のトエリスタンパク質を用いて,プロカリオトの抗ファージ防御を中和する. これらのタンパク質はシグナル分子を結合し,封じ込め,循環性オリゴヌクレオチドベースの抗ファージシグナルシステム (抗CBASS) を阻害する.

科学分野:

分子生物学
免疫学
微生物学

背景:

プロカリオット抗ファージシステムは,TIRおよびcGASのような酵素を使用して,1'-3'-グリコサイクリックADPリボース (1'-3'-gcADPR),サイクルディヌクレオチド (CDN),およびサイクルトリヌクレオチド (CTN) のようなシグナル分子を生成します.
これらのシグナル分子はファグの複製を制限するために不可欠ですが,ファグがこれらの防御に対抗するメカニズムはほとんど不明です.

研究の目的:

バクテリオファージがプロカリオット抗ファージ免疫システム,特にサイクルオリゴヌクレオチドベースの抗ファージシグナル伝達システム (アンチ-CBASS) をどのように中和させるかを調査する.
トエリスの抗防御タンパク質Tad1とTad2の抗CBASS活性抑制における分子メカニズムを解明する.

主な方法:

様々な周期性核酸 (gcADPR,CDN,CTN) に対するTad1とTad2の結合親和性を決定する生化学的測定法.
抗CBASSシステムに対するTad1とTad2の抑制活性を評価するためのin vitroおよびin vivo実験.
結合部位の構成を理解するためにTad1とTad2の構造分析.

主要な成果:

Tad1とTad2のタンパク質は,様々なサイクルヌクレオチドを同時に隔離することで,抗CBASS活性を効果的に抑制する.
Tad1はThoeris信号 (1'-3'-gcADPR, 1'-2'-gcADPR) と多数のCBASS CDNおよびCTNに対して高い親和性を示しています.
Tad1はCDN/gcADPRとCTNの独立した結合部位を有し,Tad2は異なる部位を用いて複数のサイクルヌクレオチドを結合する.

結論:

Tad1とTad2は二重作用の阻害剤として作用し,宿主の免疫を克服するファグのための新しい戦略を表しています.
これらのタンパク質は,ファージでコードされたタンパク質が柔軟な結合部位を利用して,広範囲の周期的な核酸シグナルを中和するパラダイムを確立します.
この発見はファグと宿主の相互作用と抗ファグ防御メカニズムの進化を理解するのに寄与する.

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